Imidazole → 2-(Tert-butyldimethylsilyloxy)-5-(2,3-difluorophenyl)cycloheptanol

HRID 1099157Notes

Reaction equation

HRID 1099157 reaction equation
[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:9]1[CH2:15][CH2:14][CH:13]([OH:16])[CH:12]([OH:17])[CH2:11][CH2:10]1.[Si:18](Cl)([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19].N1C=CN=C1.CCCCCC.CCOC(C)=O>CN(C=O)C.O>[Si:18]([O:17][CH:12]1[CH2:11][CH2:10][CH:9]([C:3]2[CH:4]=[CH:5][CH:6]=[C:7]([F:8])[C:2]=2[F:1])[CH2:15][CH2:14][CH:13]1[OH:16])([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 21226206Ethyl acetate hexaneHCID 579114025-(2,3-Difluorophenyl)cycloheptane-1,2-diol

Product 1

HCID 579114932-(Tert-butyldimethylsilyloxy)-5-(2,3-difluorophenyl)cycloheptanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

In a 250 mL round-bottomed flask (t=g) was added 5-(2,3-difluorophenyl)cycloheptane-1,2-diol (1.454 g, 6.0 mmol) (crude material, azeotroped with dry benzene) in DMF (20 mL) to give a colorless solution. TBS-Cl (0.995 g, 6.60 mmol) and imidazole (0.980 g, 14.40 mmol) were added, and the mixture was stirred at room temperature for 5 hours. TLC (2/1 hexane/EtOAc) indicated complete conversion to two main spots. It was diluted with water and extracted with EtOAc twice. The combined organic layers were washed with brine, dried with Na2SO4 and concentrated to a colorless oil. Purification by FCC up to 30% EtOAc/hexane afforded the desired mono-protected product as a broad peak. The product fractions were pooled and concentrated to a colorless oil (1.79 g, 84% for two steps). 1H NMR (400 MHz, CDCl3) δ 7.02-6.85 (m, 3H), 3.98-3.70 (m, 2H), 3.18-3.02 (m, 1H), 2.15-1.82 (m, 4H), 1.80-1.45 (m, 4H), 0.91 (s, 9H), 0.90 (2 s, 6H).

Workup

  1. customto give a colorless solution
  2. extractionextracted with EtOAc twice
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated to a colorless oil
  6. customPurification by FCC up to 30% EtOAc/hexane
  7. customafforded the desired mono-protected product as a broad peak
  8. concentrationconcentrated to a colorless oil (1.79 g, 84% for two steps)

Sources & evidence

ORD record
ord-57c354c4f80143a5a9d7978ef5dae57d
Source dataset
uspto-grants-2012_03
Patent number
US08143403B2

Reaction notes

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