Benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate → Benzyl 3-(diethoxyphosphorylamino)-4-methylpiperidine-1-carboxylate

HRID 1920196Notes

Reaction equation

[CH3:1][Mg]Br.[CH2:4]([O:6][P:7]([N:12]1[CH:18]2[CH:13]1[CH2:14][CH2:15][N:16]([C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20])[CH2:17]2)([O:9][CH2:10][CH3:11])=[O:8])[CH3:5]>C1COCC1.[Cu]I>[CH2:4]([O:6][P:7]([NH:12][CH:18]1[CH:13]([CH3:1])[CH2:14][CH2:15][N:16]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:17]1)([O:9][CH2:10][CH3:11])=[O:8])[CH3:5]

Participants

Conditions

Temperature: 10 °C

Procedure

To a suspension of CuI (0.3 equiv.) in anhydrous THF (0.1M) was added methyl magnesium bromide (3M solution in Et2O, 10 equiv.) at −40° C. The reaction was stirred for 30 min, followed by addition of benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate (1.0 equiv.) in THF (0.1M) at −40° C. Allowed the reaction to warm to 10° C. over 5 h, then quenched with water and extracted with ethyl acetate. The organic phase was concentrated under vacuo and purified via silica gel column chromatography eluting with ethyl acetate and hexanes (50% to 100% ethyl acetate) to yield benzyl 3-(diethoxyphosphorylamino)-4-methylpiperidine-1-carboxylate in 35% yield. LCMS (m/z): 385.0 (MH+), Rt=3.38 min.

Workup

customAllowed the reaction
customquenched with water
extractionextracted with ethyl acetate
concentrationThe organic phase was concentrated under vacuo
custompurified via silica gel column chromatography
washeluting with ethyl acetate and hexanes (50% to 100% ethyl acetate)

Sources & evidence

ORD record: ord-83df4becac904ad986a151b0bda5d188
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08168794B2

Reaction notes

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