They have to hibernate in glass coffins. The food they eat is processed into sanitized swill. Admittedly, the interior of Kubrick's spaceship is not greatly different from that of a jetliner, but at least planes go from one human environment to another. No argument that I have read for the existence of life elsewhere has maintained that other planets would be suitable for men. Kubrick makes the paradox graphic.
Space only seems large.
For human beings, it is confining. That is why, despite the size of the starry firmament, the idea of space travel gives me claustrophobia.