Trichloroacetimidic acid (S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl ester → HCID 86610907, compound

HRID 2377030Notes

Reaction equation

HRID 2377030 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[C@@H:10]([OH:20])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:21][C:22]([F:43])([F:42])[C:23]1[CH:24]=[C:25]([C@@H:33](OC(=N)C(Cl)(Cl)Cl)[CH3:34])[CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1>>[F:21][C:22]([F:42])([F:43])[C:23]1[CH:24]=[C:25]([C@H:33]([O:20][C@@H:10]2[C@@H:11]([C:13]3[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=3)[CH2:12][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9]2)[CH3:34])[CH:26]=[C:27]([C:29]([F:30])([F:31])[F:32])[CH:28]=1

Participants

3

Reactant 2

HCID 11611082Trichloroacetimidic acid (S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl esterHCID 56926702HCID 56926702, compound

Product 1

HCID 86610907HCID 86610907, compound

Procedure

The title compound was prepared from (3R,4S) tert-butyl-3-hydroxy-4-(4-fluorophenyl)pyrrolidine-1-carboxylate (Step B, Rt 13.686 min) and (1S)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl-2,2,2-trichloroethanimidoate (Example 1, step C) according to the procedure for Example 1, Step D. The product mixture was further purified by preparative HPLC on ChiralPak OD column eluting with heptanes/ethanol (98/2) to obtain the faster moving minor isomer (epimeric at the benzylic methyl position) and slower moving title compound. 1H-NMR (CDCl3): (rotamers): δ: 1.43-47 (2d, 3H, 6.5 Hz), 1.49-1.52 (2s, 9H), 3.3-3.5 (m, 3H), 3.75-3.95 (m, 3H), 4.53 (q, 1H, 6.5 Hz), 6.95 (t, 2H), 7.05 (m, 2H), 7.53 (s, 2H), 7.76 (s, 1H)ppm. MS: 466 (M-t-Bu)+ observed.

Workup

  1. customThe product mixture was further purified by preparative HPLC on ChiralPak OD column
  2. washeluting with heptanes/ethanol (98/2)
  3. customto obtain the

Sources & evidence

ORD record
ord-ea33f6df28bf42439b969ddff6dacbce
Source dataset
uspto-grants-2008_12
Patent number
US07468437B2

Reaction notes

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