4-Methyloxybenzyl chloride → HCID 66938756, compound

HRID 1911697Notes

Reaction equation

HRID 1911697 reaction equation
[C:1]([O:5][C:6](=[O:31])[NH:7][C@H:8]([C:16]1[N:17]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[C:18](Br)=[CH:19][N:20]=1)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].COC1C=CC(CCl)=CC=1>CN(C=O)C>[C:1]([O:5][C:6](=[O:31])[NH:7][C@H:8]([C:16]1[N:17]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)[CH:18]=[CH:19][N:20]=1)[CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 699934-Methyloxybenzyl chlorideHCID 66938693HCID 66938693, compound

Product 1

HCID 66938756HCID 66938756, compoundYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

{(S)-1-[5-bromo-1-(4-methoxy-benzyl)-1H-imidazol-2-yl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester: To a solution of 92C (115.0 g, 0.49 mol) in DMF (1400 mL) at 0° C. was added p-methoxybenzyl chloride (100.4 g, 0.64 mol). The reaction mixture was stirred at rt overnight, then poured into ice cold water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated. The crude was purified by column chromatography to obtain {(S)-1-[1-(4-methoxy-benzyl)-1H-imidazol-2-yl]-2-phenyl-ethyl}-carbamic acid tert-butyl ester as a white solid (120 g, 74%). 1HNMR (CDCl3, 400 MHz) δ: 7.21 (d, 2H), 7.02 (d, 2H), 6.78 (m, 6H), 6.6 (s, 1H), 5.08, 5.04 (2d, 1H), 4.64 (dd, 2H), 3.78 (s, 2H), 3.2 (m, 1H), 1.3 (m, 9H). LCMS m/z 407 (M+H)+. To this intermediate (25 g, 60 mmol) in acetonitrile at −20° C. was added N-bromosuccinimide (8.7 g, 49 mmol) portion wise and the reaction was stirred at −20° C. for 30 min. The reaction was quenched with water and extracted with ethyl acetate. The organic layer was washed with water and brine, dried over sodium sulfate and concentrated. The crude product was purified by column chromatography to give 92D as a white solid (11 g, 38%). 1HNMR (CDCl3, 400 MHz) δ 7.25 (d, 2H), 7.04 (d, 2H), 6.83 (m, 6H), 5.2 (s, 1H), 5.09 (m, 2H), 4.8 (d, 1H), 3.78 (s, 3H), 3.2 (m, 2H), 1.3 (m, 9H). LCMS m/z 486 (M+H)+.

Workup

  1. additionpoured into ice cold water
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe crude was purified by column chromatography

Sources & evidence

ORD record
ord-0bd636a17d804702b3c74a71cd5fd44e
Source dataset
uspto-grants-2013_12
Patent number
US08604056B2

Reaction notes

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