Ammonium Chloride → (R)-6-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)-2-hexanone

HRID 1050556Notes

Reaction equation

CON(C)[C:4](=[O:28])[C@H:5]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:6][CH2:7][CH2:8][NH:9][C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11].[CH3:30][Mg+].[Br-].[NH4+].[Cl-]>C1COCC1>[CH2:13]([O:12][C:10]([NH:9][CH2:8][CH2:7][CH2:6][C@@H:5]([NH:20][C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[C:4](=[O:28])[CH3:30])=[O:11])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

Conditions

Temperature: -30 °C

Procedure

N-Methoxy-N-methyl-(R)-5-(Benzyloxycarbonylamino)-2-(tert-butoxycarbonylamino)-pentanamide (305) (10 g, 24 mmol) was dissolved in THF (250 mL) and the solution was cooled to −30° C. in a dry-ice acetone bath. MeMgBr (3M in Et2O, 123 mL, 369 mmol) was added drop-wise over 30 minutes. The bath temperature was slowly allowed to increase to 0° C. and then was maintained at 0° C. until TLC showed no further reaction progress (˜80-90% complete). Saturated NH4Cl (aq) was then slowly added to the reaction mixture at 0° C. and the THF was removed under reduced pressure. The resulting aqueous solution was then extracted with EtOAc and the extracts were washed with water and then brine. The residue was then purified by column chromatography (EtOAc/hexanes) to give (R)-6-(benzyloxycarbonylamino)-3-(tert-butoxycarbonylamino)-2-hexanone (306), (6.5 g, 18 mmol, 75% yield).

Workup

temperatureto increase to 0° C.
temperaturewas maintained at 0° C. until TLC
customthe THF was removed under reduced pressure
extractionThe resulting aqueous solution was then extracted with EtOAc
washthe extracts were washed with water
customThe residue was then purified by column chromatography (EtOAc/hexanes)

Sources & evidence

ORD record: ord-96670990d15e4bcc90f8296974acea66
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09382246B2

Reaction notes

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