Triethylamine → tert-butyl ((1R,5S,6R)-5-(5-(5-chloropyridine-2-sulfonamido)-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-yl)carbamate

HRID 1526648Notes

Reaction equation

HRID 1526648 reaction equation
[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[O:9][C@H:10]2[C@@H:12]([C@:13]([C:18]3[CH:23]=[C:22]([NH2:24])[CH:21]=[CH:20][C:19]=3[F:25])([CH:15]([F:17])[F:16])[N:14]=1)[CH2:11]2)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[Cl:34][C:35]1[CH:36]=[CH:37][C:38]([S:41](Cl)(=[O:43])=[O:42])=[N:39][CH:40]=1>C(Cl)Cl.CCOC(C)=O.O>[C:1]([O:5][C:6](=[O:26])[NH:7][C:8]1[O:9][C@H:10]2[C@@H:12]([C@:13]([C:18]3[CH:23]=[C:22]([NH:24][S:41]([C:38]4[CH:37]=[CH:36][C:35]([Cl:34])=[CH:40][N:39]=4)(=[O:43])=[O:42])[CH:21]=[CH:20][C:19]=3[F:25])([CH:15]([F:17])[F:16])[N:14]=1)[CH2:11]2)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 445580985-Chloropyridine-2-sulfonyl chlorideHCID 131733175tert-butyl ((1R,5S,6R)-5-(5-amino-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-yl)carbamate

Product 1

HCID 131733176tert-butyl ((1R,5S,6R)-5-(5-(5-chloropyridine-2-sulfonamido)-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-yl)carbamateYield 70%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl((1R,5S,6R)-5-(5-amino-2-fluorophenyl)-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-3-yl)carbamate (16i-B, 0.059 g, 0.16 mmol) in DCM (1.5 mL) at 0° C. were added triethylamine (0.070 mL, 0.50 mmol) and 5-chloropyridine-2-sulfonyl chloride (0.034 g, 0.16 mmol). The reaction mixture was allowed to warm up to room temperature over a period of 2 h and then diluted with EtOAc and water. The aqueous phase was extracted with EtOAc (2×). The combined organic extracts were washed with brine and dried over MgSO4. The filtrate was concentrated under reduced pressure and the residue was purified by flash column chromatography on silica gel (10% to 50% EtOAc in heptane) to give the title compound (0.061 g, 0.11 mmol, 70% yield) as a colorless oil. MS m/z=547.0 [M+H]+. Calculated for C22H22ClF3N4O5S 546.1.

Workup

  1. extractionThe aqueous phase was extracted with EtOAc (2×)
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. customthe residue was purified by flash column chromatography on silica gel (10% to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-539915f2f1b347de93c9af3962e1e3a2
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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