Borane;tetrahydrofuran → (2-Iodo-5-(trifluoromethyl)phenyl)methanol

HRID 1028530Notes

Reaction equation

HRID 1028530 reaction equation
B.C1COCC1.[I:7][C:8]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:9]=1[C:10](O)=[O:11]>C1COCC1>[I:7][C:8]1[CH:16]=[CH:15][C:14]([C:17]([F:19])([F:20])[F:18])=[CH:13][C:9]=1[CH2:10][OH:11]

Participants

4

Reactant 2

HCID 2723981Borane;tetrahydrofuranHCID 184515332-Iodo-5-(trifluoromethyl)benzoic acid

Product 1

HCID 23160665(2-Iodo-5-(trifluoromethyl)phenyl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Borane-THF (1.0M solution in THF; 94 mL; 94 mmol) was added to a stirred solution of 2-iodo-5-(trifluoromethyl)benzoic acid (2.97 g; 9.4 mmol) in THF (300 mL) at 0° C. under N2. The reaction was heated at reflux for 90 min and then carefully quenched with 6N HCl until no further gas evolution. The reaction was diluted with H2O (250 mL) and extracted with EtOAc (3×250 mL). The combined extracts were washed with brine (300 mL), dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by flash chromatography (0-25% EtOAc/hexanes gradient) to afford [2-iodo-5-(trifluoromethyl)phenyl]methanol as a white solid. LCMS=285.0 (M−17)+. 1H NMR (CDCl3, 500 MHz): δ 7.97 (d, J=8.3 Hz, 1 H), 7.79 (s, 1 H), 7.28 (d, J=8.4 Hz, 1 H), 4.75 (s, 2 H). An alternative procedure is as follows: To a solution of 2-Iodo-5-(trifluoromethyl)benzaldehyde (EXAMPLE 80, Step A, 9 g) in THF (100 mL) and water (10 mL) at 0° C. was added NaBH4 (0.5 g). The reaction was stirred 30 minutes. To the reaction mixture was added dilute aqueous HCl (cautiously). The mixture was extracted with ether and the ether layer was washed with water, then brine. The ether layer was then dried over anhydrous MgSO4, filtered and concentrated. The material is chromatographed on SiO2 using a step gradient of 1:3 CH2Cl2/hexanes, then 1:1 CH2Cl2/hexanes, then 100% CH2Cl2 to afford [2-iodo-5-(trifluoromethyl)phenyl]methanol as a white solid.

Workup

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 90 min
  3. customcarefully quenched with 6N HCl until no further gas evolution
  4. additionThe reaction was diluted with H2O (250 mL)
  5. extractionextracted with EtOAc (3×250 mL)
  6. washThe combined extracts were washed with brine (300 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material was purified by flash chromatography (0-25% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-3472cfb2504d4da0a03c8043ad1f361c
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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