(2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylic acid → (3S)-1-[(2-fluoro-4-pyridinyl)methyl]-3-piperidinyl (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylate
Reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH2:8][N:9]2[CH2:14][CH2:13][CH2:12][C@@H:11]([OH:15])[CH2:10]2)[CH:5]=[CH:4][N:3]=1.[O:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=[C:17]1[N:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]1[C:31](O)=[O:32]>>[O:16]1[C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=2[N:18]=[C:17]1[N:25]1[CH2:30][CH2:29][CH2:28][CH2:27][C@H:26]1[C:31]([O:15][C@H:11]1[CH2:12][CH2:13][CH2:14][N:9]([CH2:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([F:1])[CH:7]=2)[CH2:10]1)=[O:32]Participants
Procedure
The title compound was prepared by a similar method to Example 36 from (3R)-1-[(2-fluoro-4-pyridinyl)methyl]-3-piperidinol [see Preparation 39] and (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylic acid [see Preparation 3]. The crude product was partly purified by column chromatography on silica gel eluting with a solvent gradient of 3:1 changing to 1:1, by volume, ethyl acetate:hexane, the product was further purified by trituration with 95:5, by volume, hot hexane:ethyl acetate, followed by trituration with hot petroleum ether:diethyl ether, 95:5 to afford (3S)-1-[(2-fluoro-4-pyridinyl)methyl]-3-piperidinyl (2S)-1-(1,3-benzoxazol-2-yl)-2-piperidinecarboxylate. The hydrochloride salt was prepared by addition of saturated hydrogen chloride gas in diethyl ether to a solution of product in ethyl acetate, and isolated as a white solid.
Workup
- customThe crude product was partly purified by column chromatography on silica gel eluting with a solvent gradient of 3:1 changing to 1:1, by volume, ethyl acetate
- customhexane, the product was further purified by trituration with 95:5, by volume, hot hexane
Sources & evidence
- ORD record
- ord-8d282b57f75d4f4295fdbce7a1aacbdd
- Source dataset
- uspto-grants-2003_05
- Patent number
- US06562964B1
Reaction notes
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