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

HRID 1662431Notes

Reaction equation

HRID 1662431 reaction equation
[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]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 57467605HCID 57467605, compoundHCID 57705631HCID 57705631, compoundHCID 57705908HCID 57705908, compound

Product 1

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

Procedure

(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.

Workup

  1. customa dark red solution formed
  2. additionThe resulting solution was filled with H2 (200 psi) three times
  3. washeluting with 1:1 hexane/EtOAc
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-3f259003277047af9a3c55760f639dbe
Source dataset
uspto-grants-2011_10
Patent number
US08030354B2

Reaction notes

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