tert-Butyl acrylate → 3-{4-[4-(4-Piperidin-1-yl-3-trifluoromethyl-phenoxymethyl)-phenyl]-piperidin-1-yl}-propionic acid

HRID 2100671Notes

Reaction equation

HRID 2100671 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[N:22]1([C:28]2[CH:33]=[CH:32][C:31](O)=[CH:30][C:29]=2[C:35]([F:38])([F:37])[F:36])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1.[C:39]([O:43]C(C)(C)C)(=[O:42])[CH:40]=C>>[N:22]1([C:28]2[CH:33]=[CH:32][C:31]([O:21][CH2:20][C:17]3[CH:16]=[CH:15][C:14]([CH:11]4[CH2:10][CH2:9][N:8]([CH2:6][CH2:40][C:39]([OH:43])=[O:42])[CH2:13][CH2:12]4)=[CH:19][CH:18]=3)=[CH:30][C:29]=2[C:35]([F:38])([F:37])[F:36])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

4

Reactant 3

HCID 15458tert-Butyl acrylateHCID 220770564-(4-Hydroxymethylphenyl)piperidine-1-carboxylic acid t-butyl esterHCID 688131284-Piperidin-1-yl-3-trifluoromethyl-phenol

Product 1

HCID 117058563-{4-[4-(4-Piperidin-1-yl-3-trifluoromethyl-phenoxymethyl)-phenyl]-piperidin-1-yl}-propionic acid

Procedure

Mitsunobu coupling of 4-(4-hydroxymethyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester and 4-Piperidin-1-yl-3-trifluoromethyl-phenol, followed by: Boc deprotection, alkylation with t-butyl acrylate, t-butyl ester deprotection, and final RP LC-MS purification as described in a previous example gave 3-{4-[4-(4-piperidin-1-yl-3-trifluoromethyl-phenoxymethyl)-phenyl]-piperidin-1-yl}-propionic acid as a tan solid. 1H NMR (DMSO-d6, 400 MHz) δ 10.25 (bs, 1H), 7.49 (d, 1H), 7.41 (d, 2H), 7.27 (d, 2H), 7.30-7.20 (m, 2H), 5.10 (s, 2H), 3.61-3.52 (m, 2H), 3.36-3.26 (m, 2H), 3.14-3.02 (m, 2H), 2.90-2.80 (m, 3H), 2.78-2.72 (m, 4H), 2.03-1.94 (m, 4H), 1.65-1.55 (m, 4H), 1.53-1.45 (m, 2H); MS (ES+): (491.2, M+1)+.

Workup

  1. customfinal RP LC-MS purification

Sources & evidence

ORD record
ord-5e235ca9b0a64c9d85ef727a30b46d80
Source dataset
uspto-grants-2009_08
Patent number
US07572811B2

Reaction notes

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