Tetrahydrofuran → (2-(2,2-Dimethylcyclopentyl)-2',5-difluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methanol

반응식

[CH3:1][C:2]1([CH3:19])[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[C:8](O)=[CH:9][C:10]([F:17])=[C:11]([CH:16]=1)[C:12](OC)=[O:13].CC1(C)CCC[C@@H]1C1[C:27](O)=[CH:28][C:29]([F:36])=C(C=1)C(OC)=O.CC1(C)C(C2C(O)=CC(F)=C(C=2)C(OC)=O)=CCC1.[CH2:58]1[CH2:62][O:61][CH2:60][CH2:59]1>>[CH3:19][C:2]1([CH3:1])[CH2:6][CH2:5][CH2:4][CH:3]1[C:7]1[CH:16]=[C:11]([CH2:12][OH:13])[C:10]([F:17])=[CH:9][C:8]=1[C:59]1[CH:58]=[C:62]([O:61][CH3:60])[CH:27]=[CH:28][C:29]=1[F:36]

참가 물질

반응물 4

HCID 8028Tetrahydrofuran

HCID 57467605HCID 57467605, 화합물

HCID 57705631HCID 57705631, 화합물

HCID 57705908HCID 57705908, 화합물

생성물 1

HCID 57705683(2-(2,2-Dimethylcyclopentyl)-2',5-difluoro-5'-(methyloxy)-1,1'-biphenyl-4-yl)methanol수율 83%

실험 절차

(R)-Methyl 5-(2,2-dimethylcyclopentyl)-2-fluoro-4-hydroxybenzoate or (S)-methyl 5-(2,2-dimethylcyclopentyl)-2-fluoro-4-hydroxybenzoate (66.44AA or 66.44AB). A mixture of Rh(COD)2BF4 (Stem Chemical) 35138-22-8, 36.95 mg, 0.091 mmol) and (R)-1-[(S)-2-(R)-(Ditertbutylphosphino)ferrocenyl]ethyl-bis-(3,5-bistrifluoromethylphenyl)phosphine (Solvias, SL-J210-1, 81.5 mg, 0.100 mmol), was stirred in THF (75 mL) under N2 for 60 minutes and a dark red solution formed. To the resulting solution was added 66.43E (8.2 g, 45.4 mmol) and TEA (10 mol %, 0.63 mL, 4.54 mmol). The resulting solution was filled with H2 (200 psi) three times and stirred at room temperature under 200 psi H2 for 2 hours. The resulting mixture was passed through a short plug of silica gel, eluting with 1:1 hexane/EtOAc and then concentrated affording the desired product as a white solid (83% yield (6.8 g), 99.3% ee). The other enantiomer may be obtained as the majority product using the enantiomer of the ferrocenyl compound.