Imidazole → (R)-ethyl 5-((tert-butyldiphenylsilyl)oxy)hexanoate

HRID 921158Notes

Reaction equation

HRID 921158 reaction equation
[OH:1][C@H:2]([CH3:11])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].N1C=CN=C1.[C:17]([Si:21](Cl)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([CH3:20])([CH3:19])[CH3:18].O>CN(C=O)C>[Si:21]([O:1][C@H:2]([CH3:11])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])([C:17]([CH3:20])([CH3:19])[CH3:18])([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 795ImidazoleHCID 962WaterHCID 94078tert-ButyldiphenylchlorosilaneHCID 11073717Ethyl 5(R)-hydroxyhexanoate

Product 1

HCID 123609631(R)-ethyl 5-((tert-butyldiphenylsilyl)oxy)hexanoateYield 80.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (R)-ethyl 5-hydroxyhexanoate (5 g, 31.2 mmol) in DMF (100 mL) at 0° C. was added imidazole (3.19 g, 46.8 mmol) followed by tert-butylchlorodiphenylsilane (12.00 mL, 46.8 mmol) and the resulting mixture was stirred at room temp for 16 h. Water (30 mL) was then added and the mixture was extracted with ether (2×100 mL). Ether layer was then washed with brine (50 mL), dried (Na2SO4), filtered and concentrated. The residue was purified via Biotage (0-10% EtOAc/hexane) to afford (R)-ethyl 5-((tert-butyldiphenylsilyl)oxy)hexanoate (10 g, 25.09 mmol, 80% yield) as clear viscous liquid. 1H NMR (500 MHz, CDCl3) δ 7.73-7.68 (m, 4H), 7.48-7.36 (m, 6H), 4.13 (q, J=7.2 Hz, 2H), 3.96-3.76 (m, 1H), 2.31-2.16 (m, 2H), 1.72-1.62 (m, 2H), 1.58-1.40 (m, 2H), 1.27 (t, J=7.1 Hz, 3H), 1.12-1.05 (m, 12H).

Workup

  1. extractionthe mixture was extracted with ether (2×100 mL)
  2. washEther layer was then washed with brine (50 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified via Biotage (0-10% EtOAc/hexane)

Sources & evidence

ORD record
ord-ff29be5524da4ae4a4378d035ff5fd3e
Source dataset
uspto-grants-2016_03
Patent number
US09273067B2

Reaction notes

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