Isobutyl chloroformate → 3-[3,5-Bis(trifluoromethyl)phenyl]-1-propanol

HRID 922874Notes

Reaction equation

HRID 922874 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[C:5]([CH:11]=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=1)[CH2:6][CH2:7][C:8](O)=[O:9].C(O)C.O.C(=O)=O.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1.O>[F:1][C:2]([F:18])([F:19])[C:3]1[CH:4]=[C:5]([CH2:6][CH2:7][CH2:8][OH:9])[CH:11]=[C:12]([C:14]([F:15])([F:16])[F:17])[CH:13]=1

Participants

7

Reactant 4

HCID 62365Isobutyl chloroformateHCID 12680983,5-Bis(trifluoromethyl)hydrocinnamic acidHCID 4311764Sodium borohydrideHCID 86603989Ethanol water dry ice

Product 1

HCID 534343813-[3,5-Bis(trifluoromethyl)phenyl]-1-propanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 3,5-bis(trifluoromethyl)hydrocinnamic acid (1.0 g, 3.5 mmol) and TEA (0.46 g, 4.5 mmol) in THF (16 mL) was cooled to −40° C. (ethanol-water/dry ice bath). To this mixture was dropwise added isobutyl chloroformate (0.56 g, 4.1 mmol) and stirring was continued for another 1.5 hours while the temperature of the cooling bath was maintained between −40° C. and −20° C. Solid NaBH4 (0.53 g, 14 mmol) was added, followed by H2O (1.3 mL). The cloudy mixture was stirred overnight while warming to room temperature. After concentrating in vacuo, the residue was partitioned between ethyl acetate and water. The aqueous layer was acidified to pH 1 with 37% HCl and extracted with ethyl acetate. The combined organic layers were washed sequentially with saturated NaHCO3, and brine, then dried (MgSO4) and concentrated. The resulting oil was purified by flash silica gel chromatography (6:4 ethyl ether-hexane) to yield 3-[3′,5′-bis(trifluoromethyl)phenyl]-1-propanol.

Workup

  1. temperaturewas maintained between −40° C. and −20° C
  2. stirringThe cloudy mixture was stirred overnight
  3. concentrationAfter concentrating in vacuo
  4. customthe residue was partitioned between ethyl acetate and water
  5. extractionextracted with ethyl acetate
  6. washThe combined organic layers were washed sequentially with saturated NaHCO3, and brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe resulting oil was purified by flash silica gel chromatography (6:4 ethyl ether-hexane)

Sources & evidence

ORD record
ord-90baadc3e9b24d4f860cbdb768a24a34
Source dataset
uspto-grants-2016_03
Patent number
US09278961B2

Reaction notes

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