Hydrochloric Acid → 2-(1-Benzenesulfonyl-1H-pyrrol-3-yl)-1-(2,3-difluoro-phenyl)-ethanone

HRID 2249513Notes

Reaction equation

[C:1]1([S:7]([N:10]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([OH:18])=O)=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]N([Si](C)(C)C)[Si](C)(C)C.COC(=O)[C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=1[F:39].Cl>C1COCC1>[C:1]1([S:7]([N:10]2[CH:14]=[CH:13][C:12]([CH2:15][C:16]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([F:38])[C:33]=3[F:39])=[O:18])=[CH:11]2)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (1-benzenesulfonyl-1H-pyrrol-3-yl)-acetic acid (1.3 g, 4.90 mmol) in THF was added LiN(TMS)2 (12 mL, 1.0M in THF, 12 mmol) at −78° C. The resulting solution was stirred at this temperature for 1 hour and 0° C. for 1 hour and then was cooled to −78° C. again. To this solution was added 2,3-difluoro-benzoic acid methyl ester (1.1 g, 6.40 mmol) and the reaction was stirred at room temperature for 14 hours. The solution was poured into 2N HCl and extracted with EtOAc. The combined organic layers were dried over MgSO4, filtered, and evaporated. The crude product was purified by flash column eluting with 20% of EtOAc in hexanes to afford the title compound as a yellow oil (1.1 g, 58%). 1H NMR (500 MHz, CDCl3) δ7.77 (d, 2H), 7.50 (m, 2H), 7.42 (t, 2H), 7.28 (m, 1H), 7.05 (m, 3H), 6.18 (m, 1H), 3.98 (s, 2H) ppm. MS (ES+): m/e=362.1 (M+H); LC/Method A/3.98 min.

Workup

temperaturewas cooled to −78° C. again
stirringthe reaction was stirred at room temperature for 14 hours
extractionextracted with EtOAc
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
customevaporated
customThe crude product was purified by flash column
washeluting with 20% of EtOAc in hexanes

Sources & evidence

ORD record: ord-d14bddca6d8e4c64a4c4f8930f0d7837
Source dataset: uspto-grants-2008_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07314885B2

Reaction notes

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