Triethylamine → benzyl chloro-6-fluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate

HRID 1943854Notes

Reaction equation

[NH2:1][C:2]1[C:3]([Cl:19])=[C:4]([C:15]([F:18])=[CH:16][CH:17]=1)[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6].C(N([CH2:25][CH3:26])CC)C.[CH2:27]([S:30](Cl)(=[O:32])=[O:31])[CH2:28][CH3:29]>ClCCl>[Cl:19][C:3]1[C:2]([N:1]([S:30]([CH2:27][CH2:25][CH3:26])(=[O:32])=[O:31])[S:30]([CH2:27][CH2:28][CH3:29])(=[O:32])=[O:31])=[CH:17][CH:16]=[C:15]([F:18])[C:4]=1[C:5]([O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:6]

Participants

Conditions

Temperature: 0 °C

Procedure

Benzyl 3-amino-2-chloro-6-fluorobenzoate (330 mg, 1.2 mmol) was dissolved in dry dichloromethane (11.8 mL). Triethylamine (0.494 mL, 3.54 mmol) was added, and the mixture was chilled to 0° C. Propane-1-sulfonyl chloride (0.332 mL, 2.95 mmol) was then added via syringe. Once the addition was complete, the mixture was allowed to warm to ambient temperature and stir for 16 hours. The mixture was diluted with dichloromethane (11 mL) and washed with water (2×50 mL) and brine (25 mL), dried over sodium sulfate, and concentrated. The resulting residue was applied directly to a silica gel column and eluted with a gradient (5% to 40%) of ethyl acetate-hexanes to provide benzyl 2-chloro-6-fluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate (413 mg, 0.840 mmol, 71.1% yield). 1H NMR (400 MHz, d6-DMSO) δ 8.00-7.94 (q, 1H), 7.59-7.52 (t, 1H), 7.50-7.35 (m, 5H), 5.48-5.44 (s, 2H), 3.80-3.60 (m, 4H), 1.89-1.75 (m, 4H), 1.05-0.98 (t, 6H).

Workup

additionOnce the addition
temperatureto warm to ambient temperature
washwashed with water (2×50 mL) and brine (25 mL)
dry with materialdried over sodium sulfate
concentrationconcentrated
washeluted with a gradient (5% to 40%) of ethyl acetate-hexanes

Sources & evidence

ORD record: ord-33ae8d0d1a164ef780cabec4b5dc2aa3
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08394795B2

Reaction notes

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