Hexamethylphosphoramide → Methyl 1-benzyl-7-methyl-2-oxoazepane-3-carboxylate

HRID 467477Notes

Reaction equation

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

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of lithium diisopropylamide in THF (1.8 M, 10 mL, 18 mmol, 1.3 equiv) freshly prepared at −78° C. was added a solution of 1-benzyl-7-methylazepan-2-one (2-3, 3.8 g, 18 mmol, 1.0 equiv) in THF (10 mL) was added. The reaction mixture was warmed to 0° C. and stirred for 1 h, then cooled to −78° C. HMPA (3.0 mL, 17 mmol, 0.99 equiv) was added followed by methyl cyanoformate (1.8 mL, 23 mmol, 1.3 equiv). After stirring 10 minutes at −78° C. the mixture was partitioned between water (40 mL) and diethyl ether (2×40 mL). The combined organic extracts were dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes gradient) to yield methyl 1-benzyl-7-methyl-2-oxoazepane-3-carboxylate (2-4). LRMS m/z (M+H) 276.2 found, 276.2 required.

Workup

additionwas added
temperaturecooled to −78° C
stirringAfter stirring 10 minutes at −78° C. the mixture
customwas partitioned between water (40 mL) and diethyl ether (2×40 mL)
dry with materialThe combined organic extracts were dried over sodium sulfate
concentrationconcentrated
customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes gradient)

Sources & evidence

ORD record: ord-3d6e5f8a6d95437ba7f8ca5da4e6c008
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08623863B2

Reaction notes

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