Triethylamine → (+/-)-Tert-butyl (6-(methylsulfonyl)-6-azaspiro[3.4]octan-8-yl)carbamate

HRID 877838Notes

Reaction equation

[CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH2:6]1[C:9]2([CH:13]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:12][NH:11][CH2:10]2)[CH2:8][CH2:7]1.C(N(CC)CC)C>C1COCC1>[CH3:1][S:2]([N:11]1[CH2:12][CH:13]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:19])([CH3:18])[CH3:20])[C:9]2([CH2:8][CH2:7][CH2:6]2)[CH2:10]1)(=[O:4])=[O:3]

Participants

Conditions

Temperature: 0 °C

Procedure

Methanesulfonyl chloride (0.073 ml, 0.939 mmol) was added dropwise to a stirred solution of (+/−)-tert-butyl 6-azaspiro[3.4]octan-8-ylcarbamate (0.177 g, 0.783 mmol) in and triethylamine (0.436 ml, 3.13 mmol) in THF (9.78 mL) @ 0° C. under N2. Stirring @ 0° C. was continued for 1.5 hr. +/−MS after 1 hr 15 min looked the same as for 40 min, mostly desired product with a trace of sm. Additional methanesulfonyl chloride (0.073 ml, 0.939 mmol) was added and stirring was continued for 50 minutes. +/−MS after 40 m indicated that the reaction had proceeded essentially to completion and no starting material was detected by mass spectrum analysis (m/e 303.4, M−H for desired product). The volatile solvents were removed under vacuum. Ethyl acetate and water were added, the organic layer was washed twice with water, followed by washing with brine, and the organic layer was separated, dried (Na2SO4), and concentrated under vacuum to yield 0.231 g of the crude product as a yellow viscous semi-solid. Flash chromatography on silica gel (Teledyne-Isco RediSep Rf 4 g column), eluting with 100 mL of 1:1 hexane:EtOAc yielded 0.197 g of the title compoud as a white solid. +/−MS: m/e 303.4 (M−H). 1H NMR (400 MHz, CHLOROFORM-d) δ 4.61 (br. s., 1H), 4.10 (br. s., 1H), 3.49 (dd, J=10.6, 5.3 Hz, 1H), 3.43-3.36 (m, 2H), 3.29 (dd, J=10.6, 3.1 Hz, 1H), 2.84 (s, 3H), 2.18-2.08 (m, 1H), 2.05-1.86 (m, 5H), 1.47 (s, 9H).

Workup

custom@ 0° C. under N2
custom+/−MS after 1 hr 15 min

Sources & evidence

ORD record: ord-3ffaea3deada4e9483b5a290b1003399
Source dataset: uspto-grants-2015_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08987268B2

Reaction notes

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