1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → (1R,3S)-(2S)-3,3,3-Trifluoro-2-methoxy-2-phenyl-propionic acid 3-(biphenyl-4-yloxy)-1-cyclohexyl ester

HRID 459119Notes

Reaction equation

[C:1]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:6]=[CH:5][C:4]([O:7][C@H:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([OH:14])[CH2:9]2)=[CH:3][CH:2]=1.[CH3:21][O:22][C@:23]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)([C:27]([F:30])([F:29])[F:28])[C:24](O)=[O:25].CCN=C=NCCCN(C)C>CN(C1C=CN=CC=1)C.ClCCl>[C:1]1([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH:6]=[CH:5][C:4]([O:7][C@H:8]2[CH2:13][CH2:12][CH2:11][C@@H:10]([O:14][C:24](=[O:25])[C@@:23]([O:22][CH3:21])([C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[C:27]([F:29])([F:30])[F:28])[CH2:9]2)=[CH:3][CH:2]=1

Participants

Conditions

Temperature: 36 °C

Procedure

A mixture of (1R*,3S*)-3-(Biphenyl-4-yloxy)-cyclohexanol from Step C (1 eq) with (S)-(−)-α-methoxy-α-(trifluoromethyl)-phenylacetic acid (1 eq), DMAP (0.1 eq) and EDCI (1.2 eq) in dichloromethane was stirred at 36° C. over night. The reaction mixture was cooled and concentrated to dryness. Reconstituted in: ether and washed with HCl 1N, and NaHCO3. Dry over MsSO4 and concentrated in vacuo to give a crude that was purified by silica gel chromatography to give a diastereomeric mixture which was separated using chiral HPLC

Workup

temperatureThe reaction mixture was cooled
concentrationconcentrated to dryness
washwashed with HCl 1N, and NaHCO3
customDry over MsSO4
concentrationconcentrated in vacuo
customto give a crude that
customwas purified by silica gel chromatography
customto give a diastereomeric mixture which
customwas separated

Sources & evidence

ORD record: ord-d431c381472f4e39838a945511b6736b
Source dataset: uspto-grants-2007_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07192982B2

Reaction notes

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