Boron trifluoride etherate → HCID 67158691, compound

HRID 1892011Notes

Reaction equation

HRID 1892011 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.C([Li])CCC.B(F)(F)F.CCOCC.[CH2:27]([O:34][CH:35]1[CH2:41][CH2:40][CH:39]2[CH:37]([O:38]2)[CH2:36]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[Cl-].[NH4+]>C1COCC1>[CH2:27]([O:34][CH:35]1[CH2:41][CH2:40][CH:39]([OH:38])[CH:37]([C:2]2[CH:3]=[CH:4][C:5]([Cl:12])=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=2)[CH2:36]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 5

HCID 8000Boron trifluoride etherateHCID 25517Ammonium ChlorideHCID 679594-Bromo-2-chloro-alpha,alpha,alpha-trifluorotolueneHCID 12827118HCID 12827118, compoundHCID 178418339Butyllithium

Product 1

HCID 67158691HCID 67158691, compoundYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of 5-bromo-2-chloro-1-trifluoromethyl-benzene (1.09 mL, 7.34 mmol) in THF (20 mL) was stirred at −78° C. and treated with n-butyllithium (1.6 M in hexane, 4.59 mL, 7.34 mmol). The resulting solution was stirred at −78° C. for 30 min and then treated with boron trifluoride etherate (924 μL, 7.34 mmol). After stirring for an additional 10 min, a solution of (1RS,3RS,6SR)-3-(benzyloxy)-7-oxa-bicyclo[4.1.0]heptane (prepared according to the procedure of Chini et al., J. Org. Chem. 1990, 55, 4265; 1.00 g, 4.90 mmol) in THF (4.0 mL) was added over a 5 min period. Upon completion of addition, the mixture was stirred at −78° C. for 70 min and then poured into saturated aqueous ammonium chloride. This mixture was extracted three times with ethyl acetate, and the combined organic phases were dried over sodium sulfate and concentrated under vacuum to yield a residue. The residue was purified by column chromatography on silica gel, eluting with 20-60% ethyl acetate-hexanes, to provide (1SR,2RS,4RS)-4-(benzyloxy)-2-(4-chloro-3-(trifluoro-methyl)phenyl)cyclohexanol as a colorless gum (958 mg, 51%). 1H NMR (400 MHz, CDCl3) δ 1.40 (bd, J=3.6 Hz, 1 H) 1.50-1.64 (m, 2 H) 1.82-1.97 (m, 2 H) 2.05-2.12 (m, 1 H) 2.12-2.20 (m, 1 H) 2.95-3.05 (m, 1 H) 3.65-3.74 (m, 1 H) 3.74-3.80 (m, 1 H) 4.54 (ab, J=12.2 Hz, 2 H) 7.27-7.40 (m, 6 H) 7.45 (d, J=8.7 Hz, 1 H) 7.55 (d, J=2.0 Hz, 1 H).

Workup

  1. stirringAfter stirring for an additional 10 min
  2. additionUpon completion of addition
  3. stirringthe mixture was stirred at −78° C. for 70 min
  4. extractionThis mixture was extracted three times with ethyl acetate
  5. dry with materialthe combined organic phases were dried over sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customto yield a residue
  8. customThe residue was purified by column chromatography on silica gel
  9. washeluting with 20-60% ethyl acetate-hexanes

Sources & evidence

ORD record
ord-45fda715d25e4f45b761bc92831ce98b
Source dataset
uspto-grants-2013_08
Patent number
US08507559B2

Reaction notes

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