Hexamethylphosphoramide → Methyl 4-benzyl-3-methyl-5-oxo-1,4-oxazepane-6-carboxylate

HRID 467486Notes

Reaction equation

C([N-]C(C)C)(C)C.[Li+].[CH2:9]([N:16]1[C:22](=[O:23])[CH2:21][CH2:20][O:19][CH2:18][CH:17]1[CH3:24])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.CN(P(N(C)C)(N(C)C)=O)C.C([C:38]([O:40][CH3:41])=[O:39])#N>C1COCC1>[CH2:9]([N:16]1[C:22](=[O:23])[CH:21]([C:38]([O:40][CH3:41])=[O:39])[CH2:20][O:19][CH2:18][CH:17]1[CH3:24])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of lithium diisopropylamide in THF (0.101 M, 100 mL, 10.1 mmol, 1.30 equiv) freshly prepared at −78° C. was added via cannula to a solution of 4-benzyl-3-methyl-1,4-oxazepan-5-one (4-3, 1.71 g, 7.80 mmol, 1 equiv) in THF (100 mL) at −78° C. and the resulting mixture was stirred for 20 min. HMPA (1.36 mL, 7.80 mmol, 1.00 equiv) was added followed by methyl cyanoformate (1.24 mL, 15.6 mmol, 2.00 equiv). The resulting mixture was warmed to 0° C., stirred for 20 min, and then partitioned between saturated aqueous ammonium chloride solution and ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (20% EtOAc in hexanes initially, grading to 100% EtOAc) to give methyl 4-benzyl-3-methyl-5-oxo-1,4-oxazepane-6-carboxylate (4-4) as a mixture of diastereomers (colorless oil). LRMS m/z (M+H) 278.2 found, 278.1 required.

Workup

stirringstirred for 20 min
custompartitioned between saturated aqueous ammonium chloride solution and ethyl acetate (2×150 mL)
dry with materialThe combined organic layers were dried over sodium sulfate
concentrationconcentrated
customThe residue was purified by flash column chromatography (20% EtOAc in hexanes initially

Sources & evidence

ORD record: ord-ac379a81bda94be3950800464294f668
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623863B2

Reaction notes

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