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 2295124Notes

Reaction equation

HRID 2295124 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>>[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

3

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%

Procedure

A solution of 2.50 g (4.9 mmol) of 2-(R)-(3,5-bis(trifluoro-methyl)benzoyloxy)-3-(S)-phenyl-4-benzyl morpholine from Example 67) and 2.50 g (12.0 mmol) of dimethyl titocene (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%).

Workup

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

Sources & evidence

ORD record
ord-797c1986e9764c398a4a4d7b35c3c417
Source dataset
uspto-grants-1997_11
Patent number
US05691336

Reaction notes

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