Ethyl Acetate → (R)-methyl 4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoate

HRID 1771162Notes

Reaction equation

F[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH2:11])(=[O:10])=[O:9])=[CH:4][C:3]=1[S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13].CC[N:21]([CH:25]([CH3:27])[CH3:26])C(C)C.[C:28]([O:31][CH2:32]C)(=[O:30])C>CN(C=O)C>[C:5]1([S:8][CH2:27][C@H:25]([NH:21][C:2]2[CH:7]=[CH:6][C:5]([S:8](=[O:10])(=[O:9])[NH2:11])=[CH:4][C:3]=2[S:12]([C:15]([F:18])([F:17])[F:16])(=[O:14])=[O:13])[CH2:26][C:28]([O:31][CH3:32])=[O:30])[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1

Participants

Conditions

Temperature: 50 °C

Procedure

4-Fluoro-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 6, 21.67 g, 71.22 mmol) and DIPEA (129 ml, 738 mmol) were added to a solution of (R)-methyl 3-amino-4-(phenylthio)butanoate, trifluoroacetic acid salt (INTERMEDIATE 7, STEP 2) in DMF (20 ml). The resulting reaction mixture was heated at 50° C. for 1.5 hours, allowed to cool to room temperature, diluted with ethyl acetate (500 ml), and washed with water (250 ml) and brine (250 ml). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (ISCO, eluting with 0→30% EtOAc/DCM over 54 minutes) to give the title product (20.5 g, yield: 56%).

Workup

customThe resulting reaction mixture
temperatureto cool to room temperature
washwashed with water (250 ml) and brine (250 ml)
dry with materialThe organic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated under reduced pressure
customThe concentrate was purified by column chromatography (ISCO, eluting with 0→30% EtOAc/DCM over 54 minutes)

Sources & evidence

ORD record: ord-243dbb3a4f1443dca3877ae081085f46
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09248140B2

Reaction notes

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