Imidazole → Methyl 4-(4-bromo-2,6-dimethylphenyl)-3-((tert-butyldimethylsilyl)oxy)butanoate

HRID 708813Notes

Reaction equation

HRID 708813 reaction equation
[Si:1](Cl)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Br:9][C:10]1[CH:15]=[C:14]([CH3:16])[C:13]([CH2:17][CH:18]([OH:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21])=[C:12]([CH3:25])[CH:11]=1.N1C=CN=C1>ClCCl.CCOC(C)=O>[Br:9][C:10]1[CH:11]=[C:12]([CH3:25])[C:13]([CH2:17][CH:18]([O:24][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])[CH2:19][C:20]([O:22][CH3:23])=[O:21])=[C:14]([CH3:16])[CH:15]=1

Participants

6

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 118098683Methyl 4-(4-bromo-2,6-dimethylphenyl)-3-hydroxybutanoate

Product 1

HCID 123665093Methyl 4-(4-bromo-2,6-dimethylphenyl)-3-((tert-butyldimethylsilyl)oxy)butanoateYield 70%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

TBS-Cl (1291 mg, 4.28 mmol) was added to a solution of 2A (860 mg, 2.86 mmol) and imidazole (389 mg, 5.71 mmol) in dichloromethane (20 mL) and stirred overnight at rt. The reaction was diluted with EtOAc, washed with water and brine, dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography (loading in chloroform, 0% to 50% ethyl acetate in hexane over 15 min using a 40 g silica gel cartridge) to yield 2B (830 mg, 1.998 mmol, 70.0% yield) as a clear oil. 1H NMR (500 MHz, chloroform-d) δ ppm 7.15 (2H, s), 4.28-4.36 (1H, m), 3.68 (3H, s), 2.82 (2H, ddd, J=53.09, 13.89, 7.02 Hz), 2.53 (2H, ddd, J=57.43, 15.06, 6.19 Hz), 2.33 (6H, s), 0.80 (9H, s), −0.10 (3H, s), −0.32 (3H, s).

Workup

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. concentrationconcentrated
  4. customThe crude product was purified by flash chromatography (loading in chloroform
  5. wait0% to 50% ethyl acetate in hexane over 15 min using

Sources & evidence

ORD record
ord-268542c68ff0443492f376b37e114c9f
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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