2-Methoxy-5-(trifluoromethoxy)benzaldehyde → 2-Methoxy-5-(trifluoromethoxy)benzyl alcohol

HRID 349247Notes

Reaction equation

HRID 349247 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:8]([O:11][C:12]([F:15])([F:14])[F:13])=[CH:7][C:4]=1[CH:5]=[O:6].[BH4-].[Na+]>CO>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:8]([O:11][C:12]([F:13])([F:15])[F:14])=[CH:7][C:4]=1[CH2:5][OH:6]

Participants

4

Reactant 2

HCID 27833642-Methoxy-5-(trifluoromethoxy)benzaldehydeHCID 4311764Sodium borohydride

Product 1

HCID 50112462-Methoxy-5-(trifluoromethoxy)benzyl alcoholYield 75.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Dissolve 2-methoxy-5-trifluoromethoxy-benzaldehyde (9.0 g, 40.9 mmol) in MeOH (100 mL) and treat with sodium borohydride (1.45 g, 38.3 mmol). Stir at RT for 1 h., then carefully quench with 1N HCl to pH 3. Concentrate, then extract the aqueous mixture with CH2Cl2 (3×100 mL). Combine the organic phases and wash with saturated NaHCO3 (100 mL) and brine (100 mL). Dry the organic layer, then filter, and concentrate. Purify the crude material by flash chromatography using a linear gradient of 100% hexanes to 40% EtOAc/hexanes to give (2-methoxy-5-trifluoromethoxy-phenyl)-methanol (6.86 g, 75%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.19 (m, 1H), 7.10 (dd, 1H, J=2.9, 8.8 Hz), 6.83 (d, 1H, J=8.8 Hz), 4.66 (d, 2H, J=6.4 Hz), 3.85 (s, 3H), 2.21 (t, 1H, J=6.4 Hz).

Workup

  1. customcarefully quench with 1N HCl to pH 3
  2. concentrationConcentrate
  3. extractionextract the aqueous mixture with CH2Cl2 (3×100 mL)
  4. washCombine the organic phases and wash with saturated NaHCO3 (100 mL) and brine (100 mL)
  5. customDry the organic layer
  6. filtrationfilter
  7. concentrationconcentrate
  8. customPurify the crude material by flash chromatography

Sources & evidence

ORD record
ord-4896a6c2c8074929a1b7a454347ed2d5
Source dataset
uspto-grants-2007_02
Patent number
US07179804B2

Reaction notes

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