ethyl 2-[3-[(1R)-3-oxocyclopentyl]-5-(trifluoromethyl)phenoxy]acetate → 2-[3-[(1R)-3-[[(1R)-1-(4-fluoro-3-methoxy-phenyl)ethyl]amino]-cyclopentyl]-5-(trifluoromethyl)phenoxy]acetic acid

HRID 1627071Notes

Reaction equation

HRID 1627071 reaction equation
O=[C:2]1[CH2:6][CH2:5][C@@H:4]([C:7]2[CH:8]=[C:9]([CH:17]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=2)[O:10][CH2:11][C:12]([O:14]CC)=[O:13])[CH2:3]1.Cl.[F:25][C:26]1[CH:31]=[CH:30][C:29]([C@H:32]([NH2:34])[CH3:33])=[CH:28][C:27]=1[O:35][CH3:36]>>[F:25][C:26]1[CH:31]=[CH:30][C:29]([C@H:32]([NH:34][CH:6]2[CH2:2][CH2:3][C@@H:4]([C:7]3[CH:8]=[C:9]([CH:17]=[C:18]([C:20]([F:21])([F:22])[F:23])[CH:19]=3)[O:10][CH2:11][C:12]([OH:14])=[O:13])[CH2:5]2)[CH3:33])=[CH:28][C:27]=1[O:35][CH3:36]

Participants

3

Reactant 2

HCID 49834558ethyl 2-[3-[(1R)-3-oxocyclopentyl]-5-(trifluoromethyl)phenoxy]acetateHCID 53484667(R)-1-(4-Fluoro-3-methoxyphenyl)ethanamine hydrochloride

Product 1

HCID 696698492-[3-[(1R)-3-[[(1R)-1-(4-fluoro-3-methoxy-phenyl)ethyl]amino]-cyclopentyl]-5-(trifluoromethyl)phenoxy]acetic acid

Procedure

General procedure A was followed using ethyl 2-[3-[(1R)-3-oxocyclopentyl]-5-(trifluoromethyl)phenoxy]acetate as the ketone and (R)-1-(4-fluoro-3-methoxyphenyl)-ethylamine hydrochloride as the amine. The resulting mixture of isomeric esters was purified and separated by flash chromatography (gradient of 0-80% EtOAc in heptane containing 2.5% NEt3). The faster eluting peak was isolated and subjected to hydrolysis following general procedure B to afford the title compound. 1H NMR (300 MHz, DMSO) δ 7.40 (d, J=8.5 Hz, 1H), 7.17 (dd, J=11.4, 8.3 Hz, 1H), 7.11-6.97 (m, 3H), 6.94 (s, 1H), 4.46 (dd, 2H), 4.10 (q, 1H), 3.84 (s, 3H), 3.16-2.86 (m, 2H), 2.21-2.07 (m, 1H), 1.94-1.58 (m, 5H), 1.45 (d, J=6.6 Hz, 3H).

Workup

  1. customwas purified
  2. customseparated by flash chromatography (gradient of 0-80% EtOAc in heptane containing 2.5% NEt3)
  3. washThe faster eluting peak
  4. customwas isolated
  5. customsubjected to hydrolysis

Sources & evidence

ORD record
ord-d15de6c11e9e41f0b16546277a772bcd
Source dataset
uspto-grants-2014_07
Patent number
US08785494B2

Reaction notes

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