Some hurdles are embodied cognition, and extended cognition.
Our bodies have many interacting levels, like the gut-brain axis where digestion and mood are linked, which may be difficult, or even undesirable, to emulate. Also our hormone systems, and evolutionary pressures we are unaware of like the proposal economic inequality increases likelihood of being violent, proposed to be adaptive in relation to competition for fewer secure niches. In terms of embodied cognition, a great deal of our biology would need to be simulated for the same kind of mind. It has been observed that we don't make aeroplanes that flap, or cars that gallop, so we might simply choose not to do this, and accept simulated minds as similar but different to organic minds.
Extended cognition relates to how the things we interact with in the world, tools like calculators, and social systems like money, augment and structure our cognitive abilities. In this sense, not only the brain would have to be emulated, but modes of interaction like hands, which shape our minds. Ultimately, this might have to involve an android or cyborg body. There would be a lot of challenges involved, not least having enough energy storage - a human brain is estimated to be equivalent to all the computing power in the world sometime around the turn of the millenium, but runs on only 20 watts - very hard to emulate! And again, we might simply choose not to do this. For instance, the human speed of physical reactions is quite slow, and we might simply prefer to allow higher speeds of interaction, even though they would produce different kinds of mind. Or we might choose to have lots of useful software, augmenting the simulated mind's skills in the way a calculator extends our own.
Mechanisms of consciousness are an issue. It's a highly speculative area, so probably not worth going too deep into details. Penrose with OrchOR suggests the Human Brain Project may be underestimating human cognitive power by at least two orders of magnitude, because of the harnessing of quantum processes in neurons. For me the really interesting point Penrose makes, is how poorly we understand memory, and that brain damage cases suggest that memory is somehow stored in a distributed way. One suggestion is memory as a kind of 'holographic image', where the whole image is stored everywhere, but each part also contributes to a higher resolution whole. See the Holonomic Brain theory. It's interesting how poorly understood memory is. I'm not stuck on these or other mechanisms, I just point at them as indicative of how the uncertainties about mechanisms likely involve many orders of magnitude, and unknown amounts of time to solve.
It's unlikely any mechanisms of consciousness generation, memory, embodied or extended cognition, pose fundamental issues for simulating human brains, because of the idea of universal computation and Turing Machines (inc quantum ones). If a series of operations can run on one machine, however complex, we expect another machine of a different type to be able to simulate it, with limitations only relating to speed.
But, these issues may pose substantial hurdles in terms of the scale of the challenge, and make it of unknown degree - for instance the energy density might make it very hard to fully localise such a brain in a human sized body. So, we can expect a long phase of not-very-human synthetic consciousness, possibly with traits or characters that make them seem more human than they really are. We might claim a brain has been uploaded, there may be subjective continuity, but the hardware would actually see it develop quite differently to if it had stayed in a body.
It's likely the phase of experimentation will fundamentally change humanity, for instance getting to experience life without the impact of hormonal cycles. We may find that a loss, in subtle ways in the long run, and simulate them. But we may not, and just as we don't expect to make aeroplanes that flap, or horses that gallop, simply embrace synthetic minds as a new thing, cultivated from human minds, but not any longer human.
Perhaps the picture of convergence and merging of human minds and Artificial General Intelligences, as advocated by for instance the Neuralink project, may be more appropriate.