Sodium hydride → 6-Benzyl-6-azaspiro[3.4]octane-5,8-dione

HRID 877718Notes

Reaction equation

[H-].[Na+].[CH2:3]([NH:10][C:11]([C:13]1([C:18](=[O:21])[CH2:19]Br)[CH2:17][CH2:16][CH2:15]C1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>C1COCC1>[CH2:3]([N:10]1[CH2:19][C:18](=[O:21])[C:13]2([CH2:17][CH2:16][CH2:15]2)[C:11]1=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium hydride (60% mineral oil dispersion) (0.366 g, 9.14 mmol) was added to a somewhat turbid solution of N-benzyl-1-(2-bromoacetyl)cyclopentanecarboxamide (2.28 g, 7.03 mmol) in THF (68.3 mL) at 0° C. under a nitrogen atmosphere during which time gas evolution was noted. Stirring @ 0° C. was continued for 55 minutes. HPLC and LC/MS after 30 minutes indicated that the reaction was essentially complete (m/e 244.19, M+H for desired product; no sm detected). The reaction, was maintained at 0° C., diluted with EtOAc (100 mL) and 40 mL of sat. aq NH4Cl solution, and finally 40 mL of water. The layers were separated, the organic layer was washed with 40 mL of water, and 40 mL of brine, the organic layer was dried over Na2SO4, and concentrated under vacuum to yield 1.86 g of a tan viscous oil. Flash chromatography on silica gel (Teledyne-Isco RediSep Rf 40 g column), eluting with 100 mL of 95:5, 400 mL of 90:10, and 300 mL of 80:20 hexane:EtOAc yielded 1.44 g of the title compound as a viscous pale yellow oil. LC/MS: m/e 244.16 (M+H), 276.2 (M+H+methanol, hemiacetal formation). +/−MS: m/e 244.2 (M+H), 242.4 (M−H). 1H NMR (400 MHz, CHLOROFORM-d) δ 7.41-7.23 (m, 5H), 4.64 (s, 2H), 3.69 (s, 2H), 2.10-1.97 (m, 2H), 1.97-1.81 (m, 6H).

Workup

waitHPLC and LC/MS after 30 minutes indicated that the reaction

Sources & evidence

ORD record: ord-db85415189e344b1a307ff7f52a696c8
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987268B2

Reaction notes

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