2-(R)-(3,5-Bis(trifluoromethyl)benzoyloxy)-3-(S)-phenyl-4-benzyl Morpholine → 2-(R)-(1-(3,5-Bis(trifluoromethyl)-phenyl)ethenyloxy)-3-(S)-phenyl-4-benzyl morpholine

HRID 1956501Notes

Reaction equation

HRID 1956501 reaction equation
[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([CH:28]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:30]=1)[C:6]([O:8][C@H:9]1[O:14][CH2:13][CH2:12][N:11]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C@H:10]1[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)=O.[CH2:37]1COCC1.C1(C)C=CC=CC=1>C[C-]1C=CC=C1.[C-]1(C)C=CC=C1.[Ti+2]>[F:1][C:2]([F:36])([F:35])[C:3]1[CH:4]=[C:5]([C:6]([O:8][C@H:9]2[O:14][CH2:13][CH2:12][N:11]([CH2:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[C@H:10]2[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH2:37])[CH:28]=[C:29]([C:31]([F:33])([F:32])[F:34])[CH:30]=1

Participants

4

Reactant 2

HCID 105296672-(R)-(3,5-Bis(trifluoromethyl)benzoyloxy)-3-(S)-phenyl-4-benzyl MorpholineHCID 22635083Tetrahydrofuran toluene

Product 1

HCID 106492802-(R)-(1-(3,5-Bis(trifluoromethyl)-phenyl)ethenyloxy)-3-(S)-phenyl-4-benzyl morpholineYield 69%

Reagents, catalysts & solvents 1

HCID 129651941Dimethyl titanoceneCatalyst

Procedure

A solution of 2.50 g (4.9 mmol) of 2-(R)-(3,5-bis(tri-fluoro-methyl)benzoyloxy)-3-(S)-phenyl-4-benzyl morpholine (from Example 67) and 2.50 g (12.0 mmol) of dimethyl titanocene (from Example 68, Step A) in 35 mL of 1:1 v/v THF/toluene was stirred in an oil bath at 80° C. for 16 hours. The reaction mixture was cooled and concentrated in vacuo. Flash chromatography on 150 g of silica gel using 3:1 v/v hexanes/methylene chloride as the eluant afforded 1.71 g (69%) of the title compound as a solid. Alternatively, the product may be isolated by crystallization from methanol, following precipitation of titanium residues. Mass Spectrum (FAB): m/Z 508 (M+H, 25%). 1H NMR (CDCl3, 400 MHz, ppm): δ 2.42 (dt, J=3.6, 12.0, 1H), 2.89 (app d, J=11.6), 2.92 (d, J=13.6, 1H), 3.61-3.66 (m, 1H), 3.73 (d, J=2.8), 1H), 4.00 (d, J=13.6, 1H), 4.09 (dt, J=2.4, 11.6, 1H), 4.75 (d, J=2.8, 1H), 4.79 (d, J=2.8, 1H), 5.36 (d, J=2.4, 1H), 7.23-7.41 (m, 7H), 7.63 (app d, J=7.2, 2H), 7.79 (s, 1H), 7.91 (s, 2H). Analysis Calcd for C27 H23F6NO2 : C, 63.90; H, 4.57; N, 2.76; F, 22.46. Found: C, 63.71; H, 4.53; N, 2.68; F, 22.66.

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-755d6111eee44a619a040d79c4b78850
Source dataset
uspto-grants-1998_07
Patent number
US05780467

Reaction notes

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