Methanesulfonyl chloride → 2-(Tert-butoxycarbonylamino)-2-(4-chlorophenyl)ethyl methanesulfonate

HRID 423042Notes

Reaction equation

[CH3:1][S:2](Cl)(=[O:4])=[O:3].[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([CH:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:14][OH:15])=[CH:9][CH:8]=1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH3:1][S:2]([O:15][CH2:14][CH:13]([NH:16][C:17]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:23])[C:10]1[CH:11]=[CH:12][C:7]([Cl:6])=[CH:8][CH:9]=1)(=[O:4])=[O:3]

Participants

Conditions

Temperature: 0 °C

Procedure

Methanesulfonyl chloride (1.451 mL, 18.74 mmol) was added to tert-butyl 1-(4-chlorophenyl)-2-hydroxyethylcarbamate (4.63 g, 17.04 mmol) and N,N-diisopropylethylamine (6.23 mL, 35.78 mmol) in DCM (40 mL) cooled to 0° C. over a period of 5 minutes under nitrogen. The resulting solution was stirred at 20° C. for 2 hours. The reaction mixture was diluted with DCM (100 mL) and washed sequentially with water (100 mL). The organic layer was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% EtOAc in DCM. Pure fractions were evaporated to dryness to afford 2-(tert-butoxycarbonylamino)-2-(4-chlorophenyl)ethyl methanesulfonate (3.12 g, 52.3%) as a white solid. 1H NMR (399.9 MHz, DMSO-d6) δ 1.39 (9H, s), 3.17 (3H, s), 4.22-4.28 (2H, m), 4.90 (1H, d), 7.40-7.46 (4H, m), 7.68 (1H, d). m/z (ESI+) (M−H)−=348; HPLC tR=2.32 min.

Workup

washwashed sequentially with water (100 mL)
dry with materialThe organic layer was dried over MgSO4
filtrationfiltered
customevaporated
customto afford crude product
customThe crude product was purified by flash silica chromatography, elution gradient 0 to 10% EtOAc in DCM
customPure fractions were evaporated to dryness

Sources & evidence

ORD record: ord-d80bcc75aae44604b3fe4ba38de04971
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08101623B2

Reaction notes

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