Hydrochloric Acid → (3-Chloro-5-(trifluoromethyl)phenyl)methanol

HRID 391380Notes

Reaction equation

HRID 391380 reaction equation
N[C:2]1[CH:3]=[C:4]([CH2:12][OH:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.N(OC(C)(C)C)=O.[ClH:21]>C(#N)C.[Cu](Cl)Cl>[Cl:21][C:2]1[CH:3]=[C:4]([CH2:12][OH:13])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10906Tert-Butyl nitriteHCID 53414333(3-Amino-5-(trifluoromethyl)phenyl)methanol

Product 1

HCID 3857254(3-Chloro-5-(trifluoromethyl)phenyl)methanol

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 6342AcetonitrileSolvent2×

Procedure

(3-Amino-5-(trifluoromethyl)phenyl)methanol (1.0 g, 5.23 mmol) in dry acetonitrile (6 mL) was added dropwise to a solution of copper (II) chloride (0.83 g, 6.2 mmol) and tert-butyl nitrite (0.9 mL, 7.5 mmol) in acetonitrile (6 mL) at 65° C. After 30 min at 65° C., the reaction mixture was cooled to room temperature, poured into a 1 N hydrochloric acid solution, and extracted with ethyl acetate (2×). The organic layers were pooled together, washed with brine (2×), dried over sodium sulfate, and concentrated. Column chromatography on silica gel (30% ethyl acetate/hexanes) afforded 0.8 g (73%). 1H-NMR (CDCl3, 500 MHz) δ 7.54 (s, 1H), 7.52 (s, 1H), 7.50 (s, 1H), 4.74 (s, 2H).

Workup

  1. extractionextracted with ethyl acetate (2×)
  2. washwashed with brine (2×)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customColumn chromatography on silica gel (30% ethyl acetate/hexanes) afforded 0.8 g (73%)

Sources & evidence

ORD record
ord-4bbfea6f864c43fd86044d4dbeda98e5
Source dataset
uspto-grants-2013_02
Patent number
US08383821B2

Reaction notes

Loading…