N,O-Dimethylhydroxylamine → 1,1-Dimethylethyl N-((1S)-2-(methoxymethylamino)-2-oxo-1-(phenylmethyl)ethyl)carbamate

HRID 649728

Reaction equation

[NH:1]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:2]([C:10]([OH:12])=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:20][NH:21][O:22][CH3:23].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>C(Cl)Cl>[CH3:23][O:22][N:21]([CH3:20])[C:10](=[O:12])[C@H:2]([CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1)[NH:1][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of Boc-Phe-OH 5.1 (2.0 g, 7.53 mmol) and N,O dimethylhydroxylamine (808 mg, 8.29 mmol) in DCM (38 ml) was added TEA (2.2 ml, 15.8 mmol) and HOBT (1.27 g, 8.29 mmol). After cooling to 0° C., EDCI (1.59 g, 8.29 mmol) was added in one portion, and the reaction was stirred overnight, warming to room temperature. The reaction was concentrated in vacuo, diluted with EthOAc (150 ml), and washed with H2O, 1 N KHSO4, 1 N NaHCO3 and brine. After drying over Na2SO4, filtering, and concentrating in vacuo, the residue was purified by flash chromatography to give the title compound as an oil in 88% yield. Rf=0.35 (50% EthOAc/hexane). 1H NMR (300 MHz, CDCl3) δ7.28 (d, 2H, J=7.4 Hz), 7.24 (t, 1H, J=6.8 Hz), 7.17 (d, 2H, 7.1 Hz), 5.18 (d, 1H, J=7.4 Hz), 4.9 (dd, 1H, J=7.0, 11.9 Hz), 3.66 (s, 3H), 3.16 (s, 3H), 3.05 (dd, 1H, J=6.0, 13.6 Hz), 2.87 (dd, 1H, J=7.0, 13.6 Hz), 1.39 (s, 9H).

Workup

temperaturewarming to room temperature
concentrationThe reaction was concentrated in vacuo
additiondiluted with EthOAc (150 ml)
washwashed with H2O, 1 N KHSO4, 1 N NaHCO3 and brine
dry with materialAfter drying over Na2SO4
filtrationfiltering
concentrationconcentrating in vacuo
customthe residue was purified by flash chromatography

Sources & evidence

ORD record: ord-bd070c42e5024da69a098affb66e5c43
Source dataset: uspto-grants-2001_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06270957B1

Linked notes

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