Imidazole → 2-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethane

HRID 2261420Notes

Reaction equation

HRID 2261420 reaction equation
[CH3:1][C:2]([Si:5](Cl)([CH3:7])[CH3:6])([CH3:4])[CH3:3].N1C=CN=C1.[Br:14][CH2:15][C@@H:16]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:20]([NH:32][CH:33]=[O:34])[CH:19]=1)[OH:17]>C(Cl)Cl>[Br:14][CH2:15][C@H:16]([O:17][Si:5]([C:2]([CH3:4])([CH3:3])[CH3:1])([CH3:7])[CH3:6])[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[C:20]([NH:32][CH:33]=[O:34])[CH:19]=1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 11142645(R)-N-[5-(2-Bromo-1-hydroxyethyl)-2-(phenylmethoxy)phenyl]formamide

Product 1

HCID 574610672-bromo-(R)-1-tert-butyldimethylsiloxy-1-(3-formamido-4-benzyloxyphenyl)ethaneYield 91.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of TBDMS-Cl (40.1 g, 0.26 mol) in DCM (37.5 mL) was added to a slurry of imidazole (21.86 g, 0.32 mol) and (R)-2-bromo-1-(3-formamido-4-benzyloxyphenyl)ethanol (74.54 g, 0.21 mol) in DCM (260 mL) over 8 minutes. The mixture was stirred for 22 hours. The reaction was quenched with water (190 mL) and the aqueous layer was extracted with DCM (37.5 mL). The combined DCM layers were distilled at atmospheric pressure to a volume of ca. 110 mL. On cooling, spontaneous crystallisation occurred. Isooctane (750 mL) was added dropwise over 20 minutes. The slurry was cooled to 0° C. and the solids were collected by filtration then washed with 9:1 v/v isooctane:DCM (3×75 mL) and dried in vacuo to give the title compound as a colourless solid (89.65 g, 90% th). 1H NMR in accord with structure (400 MHz, CDCl3) δ(ppm): −0.06 (3H) s; 0.11 (3H) s; *0.12 (3H) s; *0.89 (9H) s; 0.90 (9H) s; *3.38-3.49 (2H) m; 4.78-4.87 (1H) m; *5.09 (2H) s; 5.10 (2H) s; 6.96 (1H) d, J=8.6 Hz; *7.06 (1H) d of d, J=8.3, 2.0 Hz; 7.11 (1H) d of d, J=8.3 Hz, 2.0 Hz; 7.25-7.27 (1H) m; 7.36-7.45 (5H) m; *7.70 (1H) d, J=11.0 Hz; 7.79 (1H) s; 8.38 (1H) d, J=2.0 Hz; 8.42 (1H) d, J=1.5 Hz; *8.76 (1H) d, J=11.8 Hz. *Peaks are due to ca 25M % of the minor rotamer.

Workup

  1. customThe reaction was quenched with water (190 mL)
  2. extractionthe aqueous layer was extracted with DCM (37.5 mL)
  3. distillationThe combined DCM layers were distilled at atmospheric pressure to a volume of ca. 110 mL
  4. temperatureOn cooling
  5. customspontaneous crystallisation
  6. additionIsooctane (750 mL) was added dropwise over 20 minutes
  7. filtrationthe solids were collected by filtration
  8. washthen washed with 9:1 v/v isooctane
  9. dry with materialDCM (3×75 mL) and dried in vacuo

Sources & evidence

ORD record
ord-9ff6a7834c93445387e517fdf52e0d3f
Source dataset
uspto-grants-2010_12
Patent number
US07846973B2

Reaction notes

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