Methyl 3-aminopropanoate hydrochloride → (+/-)-3-({5-[1-(2,6-Dimethyl-4'-trifluoromethyl-biphenyl-4-yloxymethyl)-propyl]-thiophene-2-carbonyl}-amino)-propionic acid methyl ester
Reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1.CO[C:22]([C:24]1[S:25][C:26]([CH:29]([CH2:32]O)[CH2:30][CH3:31])=[CH:27][CH:28]=1)=[O:23].Cl.[CH3:35][O:36][C:37](=[O:41])[CH2:38][CH2:39][NH2:40]>>[CH3:35][O:36][C:37](=[O:41])[CH2:38][CH2:39][NH:40][C:22]([C:24]1[S:25][C:26]([CH:29]([CH2:32][O:8][C:6]2[CH:5]=[C:4]([CH3:9])[C:3]([C:10]3[CH:15]=[CH:14][C:13]([C:16]([F:18])([F:17])[F:19])=[CH:12][CH:11]=3)=[C:2]([CH3:1])[CH:7]=2)[CH2:30][CH3:31])=[CH:27][CH:28]=1)=[O:23]Participants
Reactant 3
Product 1
Procedure
This compound is made by the general method as exemplified in Preparation 94 using 2,6-dimethyl-4′-trifluoromethyl-biphenyl-4-ol and 5-(1-hydroxymethyl-propyl)-thiophene-2-carboxylic acid methyl ester in Step A and 3-amino-propionic acid methyl ester hydrochloride salt in Step C as the starting materials to provide (±)-3-({5-[1-(2,6-dimethyl-4′-trifluoromethyl-biphenyl-4-yloxymethyl)-propyl]-thiophene-2-carbonyl}-amino)-propionic acid methyl ester (0.225 g) as a white solid. MS (ES): 532.3 [M−H]−. The racemic material is separated by chiral HPLC (column: Chiralpak AD-H 4.6×150 mm; eluent: 20:80 IPA/supercritical CO2; flow rate: 5 mL/min; UV absorbance wavelength: 270 nm) to provide Isomer 1 (0.049 g, >99% ee) and Isomer 2 (0.049 g, 96.8% ee).
Sources & evidence
- ORD record
- ord-435980b2ad514db7ad01cfa67904ca64
- Source dataset
- uspto-grants-2011_12
- Patent number
- US08084489B2
Reaction notes
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