The Royals went ahead in the fourth minute when Pavel Pogrebnyak scored in his second successive game but the lead lasted just over four minutes.
The impressive Gylfi Sigurdsson crossed for Michael Dawson to score his first league goal since February 2011 and Spurs then took control of the game thanks to strikes from Emmanuel Adebayor and Clint Dempsey.
"I couldn't fault our players," McDermott said. "The discipline of the team, you have to come here with a certain way of playing and I thought we were going to get something.
"You'd take a goal any time, it was a great free-kick and Pavel scored on the rebound."
Pogrebnyak's early effort was his fourth league goal of the season but the Russian striker missed a glorious chance to level the match at 2-2 when he headed wide after Hugo Lloris had parried his initial shot.
"We had three opportunities at 2-1, if we'd got the second goal it could have gone either way," he said.
"It is disappointing that one of the chances didn't go in, they were good opportunities - it wasn't really a 3-1 game, that didn't really tell the story of the game."
McDermott also hailed Spurs, saying: "They had plenty of possession, Andre has put a good side together, it has been building for a while, they have a really good chance - they're going to finish very, very high in this league."