Water → (2S,3S)-2-(3,5-Bis-trifluoromethyl-benzyloxy)-3-phenyl-morpholine

HRID 862422Notes

Reaction equation

HRID 862422 reaction equation
C([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([O:14][CH2:15][C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)[C@@H:9]1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)C1C=CC=CC=1.O.[H][H]>C(O)C.[Pd]>[F:29][C:26]([F:27])([F:28])[C:18]1[CH:17]=[C:16]([CH:21]=[C:20]([C:22]([F:23])([F:24])[F:25])[CH:19]=1)[CH2:15][O:14][C@H:10]1[O:11][CH2:12][CH2:13][NH:8][C@H:9]1[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 3

HCID 962WaterHCID 107438244-benzyl-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenylmorpholineHCID 178418361HCID 178418361, compound

Product 1

HCID 9887525(2S,3S)-2-(3,5-Bis-trifluoromethyl-benzyloxy)-3-phenyl-morpholineYield 80%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of 0.68 g of 4-benzyl-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(S)-phenylmorpholine and 280 mg of 10% Pd/C in 36 ml of 97:3 ethanol:water was stirred under one atmosphere of hydrogen for 15 hr. The mixture was filtered through Celite, the filter cake was washed generously with ethanol, and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on 68 g of silica eluting with 1 L of 33:67 hexanes:diethyl ether, then 1 L of 25:75 hexanes:diethyl ether to give 0.443 g (80%) of an oil, which by 1H NMR was pure cis morpholine. 1H NMR (400 MHz, CDCl3) δ 1.8 (1H, br s), 3.10 (1H, dd, J=12.5, 2.9 Hz), 3.24 (1H, td, J=12.2, 3.6 Hz), 3.62 (1H, dd, J=11.3, 2.5 Hz), 4.04 (1H, td, J=11.7, 3 Hz), 4.11 (1H, d, J=2.4Hz), 4.49 (1H, d, J=13.5 Hz), 4.74 (1H, d, J=2.5 Hz), 4.80 (1H, d, J=13.3 Hz), 7.25-7.40 (5H, m), 7.40 (2H, s), 7.68 (1H, s). Anal. Calcd. For C19H17F6NO2 : C, 56.30; H, 4.23; N, 3.46; F, 28.12. Found: C, 56.20; H, 4.29; N, 3.34; F, 27.94.

Workup

  1. filtrationThe mixture was filtered through Celite
  2. washthe filter cake was washed generously with ethanol
  3. concentrationthe filtrate was concentrated in vacuo
  4. customThe residue was purified by flash chromatography on 68 g of silica eluting with 1 L of 33:67 hexanes

Sources & evidence

ORD record
ord-d73a779d1b064233927e4197fd454ffd
Source dataset
uspto-grants-1998_02
Patent number
US05719149

Reaction notes

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