Borane → [5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanol

HRID 1994466Notes

Reaction equation

HRID 1994466 reaction equation
B.[CH:2]([C:5]1[CH:6]=[CH:7][C:8]([O:24][CH3:25])=[C:9]([C:11]2[C:12]([C:21](O)=[O:22])=[CH:13][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:15][CH:16]=2)[CH:10]=1)([CH3:4])[CH3:3].C(C1C=CC(OC)=C(C2C(C(N)=O)=CC(C(F)(F)F)=CC=2)C=1)(C)C>C1COCC1>[CH:2]([C:5]1[CH:6]=[CH:7][C:8]([O:24][CH3:25])=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:13][C:12]=2[CH2:21][OH:22])[CH:10]=1)([CH3:4])[CH3:3]

Participants

5

Reactant 3

HCID 6331BoraneHCID 533636465'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-carboxylic acidHCID 667165875'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-carboxamide

Product 1

HCID 53363647[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of borane in THF (1 M, 859 μL, 0.859 mmol) was added dropwise to a stirred solution of 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carboxylic acid and 5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-carboxamide (3:1, 96.8 mg, 0.286 mmol) in dry THF at room temperature under N2. The reaction was stirred at room temperature for 3 h and carefully quenched with water (10 mL). The mixture was extracted with EtOAc (3×20 mL) and the combined extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo to give the crude product. This was purified by flash chromatography (Si, 125×160 mm, 0-30% EtOAc in hexanes gradient) to afford [5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanol as a colorless oil. Rf=0.27 (10% EtOAc/hexanes). 1H NMR (CDCl3, 500 MHz) δ 7.89 (br s, 1H), 7.62 (dd, J=8.0, 1.3 Hz, 1H), 7.36 (d, J=8.0 Hz, 1H), 7.29 (dd, J=8.5, 2.3 Hz, 1H), 7.03 (d, J=2.3 Hz, 1H), 6.96 (d, J=8.5, 1H), 4.51 (m, 2H), 3.74 (s, 3H), 2.93 (septet, J=7.0 Hz, 1H), 2.51 (s, 1H), 1.29 (d, J=7.0 Hz, 6H).

Workup

  1. customcarefully quenched with water (10 mL)
  2. extractionThe mixture was extracted with EtOAc (3×20 mL)
  3. washthe combined extracts were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customto give the crude product
  7. customThis was purified by flash chromatography (Si, 125×160 mm, 0-30% EtOAc in hexanes gradient)

Sources & evidence

ORD record
ord-80692e6d8e944b62ac57bef17f79b60d
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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