Imidazole → (5S)-5,7-Bis-{[tert-butyldimethylsilyl)oxy]}-4,4-dimethylheptan-3-one

HRID 1367674Notes

Reaction equation

HRID 1367674 reaction equation
[BH4-].[Na+].[C:3]([Si:7]([CH3:21])([CH3:20])[O:8][C@H:9]([C:13]([CH3:19])([CH3:18])[C:14](=[O:17])[CH2:15][CH3:16])[CH2:10][CH:11]=[O:12])([CH3:6])([CH3:5])[CH3:4].N1C=CN=C1.[Si:27](Cl)([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].[Cl-].[NH4+]>C(Cl)Cl.O.C(O)C>[C:3]([Si:7]([CH3:20])([CH3:21])[O:8][C@@H:9]([CH2:10][CH2:11][O:12][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28])[C:13]([CH3:19])([CH3:18])[C:14](=[O:17])[CH2:15][CH3:16])([CH3:5])([CH3:4])[CH3:6]

Participants

9

Reactant 5

HCID 795ImidazoleHCID 25517Ammonium ChlorideHCID 28928tert-Butyldimethylsilyl chlorideHCID 4311764Sodium borohydrideHCID 15331379(3S)-3-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]-4,4-dimethyl-5-oxoheptanal

Product 1

HCID 9909110(5S)-5,7-Bis-{[tert-butyldimethylsilyl)oxy]}-4,4-dimethylheptan-3-oneYield 81%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent4×

Procedure

Sodium borohydride (570 mg, 15.4 mmol, 2 equiv) was dissolved in methylene chloride (175 ml) and dry ethanol (75 ml). The mixture was cooled to −78° C. for 15 min after which a solution of aldehyde 76 (2.2 g, 7.7 mmol, 1 equiv) in methylene chloride (5 ml) was added. After stirring for 1 h water (6 ml) was added and the reaction mixture was allowed to warm to room temperature. Methylene chloride (400 ml) was added and the mixture was washed with saturated aqueous sodium bicarbonate before it was dried over anhydrous sodium sulfate and concentrated in vacuo to give crude alcohol mixture 77 and 78. The crude alcohol mixture was dissolved in methylene chloride (40 ml) and cooled to 0° C. Imidazole (3.14 g, 46.15 mmol, 6 equiv) and tert-butyldimethylsilyl chloride (3.47 g, 23.1 mmol, 3 equiv) were added and the reaction mixture was stirred at room temperature for 16 hr. Saturated aqueous ammonium chloride (30 ml) was added and the layers were separated. The aqueous layer was further extracted with ethyl acetate (3×30) and combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash chromatography (1%-5% EtOAc/Hexanes) gave the bis(silylether) 68 (2.5 g, 81% over two steps) as a colorless oil: [α]22D=−7.4 (c=1.8, CHCl3); TLC Rf=0.70 (silica gel, 20% EtOAc/hexanes); 1H NMR (600 MHz, CDCl3) δ 4.058-4.022 (dd, 1H), 3.62-3.54 (m, 2H), 2.57-2.50 (dq, 1H), 2.48-2.40 (dq, 1H), 1.53-1.41 (m, 2H), 1.085 (s, 3H), 1.022 (s, 3H), 0.985-0.96 (t, 3H), 0.86-0.85 (d, 18H), 0.067 (s, 3H), 0.018 (s, 3H), 0.013 (s, 3H), 0.002 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 215.783, 73.613, 60.286, 53.247, 37.458, 31.76, 26.276, 26.116, 22.386, 20.199, 18.533, 18.441, 7.941, −3.805, −3.834, −5.105; HRMS calcd for C21H46O3Si2+Na+ 425.2883; found 425.2885 [M+Na+].

Workup

  1. additionwas added
  2. additionwas added
  3. washthe mixture was washed with saturated aqueous sodium bicarbonate before it
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customto give crude alcohol mixture 77 and 78
  7. temperaturecooled to 0° C
  8. customthe layers were separated
  9. extractionThe aqueous layer was further extracted with ethyl acetate (3×30)
  10. dry with materialwere dried over anhydrous sodium sulfate
  11. concentrationconcentrated in vacuo
  12. customPurification by flash chromatography (1%-5% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-a01beb0399824836b0b92ccb5dc530ea
Source dataset
uspto-grants-2011_02
Patent number
US07893268B2

Reaction notes

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