tert-butyl (1R,5S)-3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate → 3-Methylene-8-Boc-8-Azabicyclo[3.2.1]Octane

HRID 1849583Notes

Reaction equation

[Li][CH2:2][CH2:3][CH2:4][CH3:5].O=C1[CH2:13][C@H:12]2[N:14]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C@H]([CH2:10][CH2:11]2)C1>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[CH2:5]=[C:4]1[CH2:13][CH:12]2[N:14]([C:15]([O:17][C:18]([CH3:20])([CH3:19])[CH3:21])=[O:16])[CH:2]([CH2:10][CH2:11]2)[CH2:3]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of methyltriphenylphosphonium bromide (2.38 g, 6.6 mmol) in dry THF at 0° C. was added n-BuLi (2.7 mL, 2.5 M) dropwise. After stirring at 0° C. for 30 min, (1R,5S)-tert-butyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate (500 mg, 2.2 mmol) was added and the mixture was stirred at 0° C. for additional 16 hrs. The reaction was quenched by sat. NH4Cl and extracted with EtOAc (50 mL×3) and purified by SGC (eluting with petroleum ether/ethyl acetate=20/1) to give target compound (130 mg, 27%). 1H NMR (500 MHz, CDCl3) δ4.77 (t, J=4.0 Hz, 2H), 4.21 (br s, 1H), 4.11 (br s, 1H), 2.43-2.33 (m, 2H), 2.01 (s, 1H), 1.98 (s, 1H), 1.79 (d, J=3.0 Hz, 2H), 1.53-1.49 (m, 2H), 1.43 (s, 9H).

Workup

stirringthe mixture was stirred at 0° C. for additional 16 hrs
customThe reaction was quenched by sat. NH4Cl
extractionextracted with EtOAc (50 mL×3)
custompurified by SGC (eluting with petroleum ether/ethyl acetate=20/1)

Sources & evidence

ORD record: ord-fb0b9e6c51124d8dafbcf010de1e2678
Source dataset: uspto-grants-2015_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08952169B2

Reaction notes

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