I think it will be fine, as long as he is well-trained not to open the door to anyone and to stay in the room and not come looking for you... EXCEPT ... in the case of a fire alarm going off.
This is something that you should always do with kids in hotels, and even without kids. The fire exit map should be on the inside of the room door, and you should not only look at it carefully, but walk the route if you have kids with you. It's REALLY rare to have a hotel fire in the US, but they are serious business, and should be prepared for. Kids are trained about fire evacuations in school; if he knows what to do, he will almost surely do it exactly as he should. (This has been tested by airlines -- they found that adults often lose it and get confused and dithery when told to evacuate a plane, but school-aged kids always follow the rules just as they are told to.)
I learned my lesson on this after an incident in the UK. We had been on a flight that got in late, and had trouble finding the hotel, so we did not get checked in until nearly one am. Naturally, at that time of night we didn't bother to look at the evac map. Sure enough, an alarm went off at 2:30 am, and we had to evacuate. Luckily, it was a false alarm and there was no smoke in the halls. DS didn't even wake up that time; we just carried him.
Also, since we are talking about going out in the wee hours while he is sleeping, always leave a note, and carry your cell phone, not so much for his safety, as for yours, so that you can get in touch if something delays you. I once forgot my cell phone in the car after checking into a hotel on a road trip, and decided to run down to get it at 11 pm -- while my family was sleeping. I took the stairs down, and I got locked in the blasted stairwell! (Really locked in, not just only having the option of setting off an alarm. The crash-barred fire doors were all locked with keyed deadbolts!) I banged on doors and shouted for an hour before someone heard me. If I had stayed there until morning, DH and DS would have had absolutely no idea of where I was or what had happened to me (and in that particular case, I probably would have died -- it was winter and the stairwell was unheated.)