Trifluoroacetic acid → N-(3-((1R,5S,6R)-3-amino-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-5-chloropyridine-2-sulfonamide

HRID 1526649Notes

Reaction equation

HRID 1526649 reaction equation
C(OC(=O)[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:25]([C:28]4[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][N:29]=4)(=[O:27])=[O:26])[CH:21]=[CH:20][C:19]=3[F:35])([CH:15]([F:17])[F:16])[N:14]=1)[CH2:11]2)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:7][C:8]1[O:9][C@H:10]2[C@@H:12]([C@:13]([C:18]3[CH:23]=[C:22]([NH:24][S:25]([C:28]4[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][N:29]=4)(=[O:26])=[O:27])[CH:21]=[CH:20][C:19]=3[F:35])([CH:15]([F:16])[F:17])[N:14]=1)[CH2:11]2

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 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)carbamate

Product 1

HCID 90401360N-(3-((1R,5S,6R)-3-amino-5-(difluoromethyl)-2-oxa-4-azabicyclo[4.1.0]hept-3-en-5-yl)-4-fluorophenyl)-5-chloropyridine-2-sulfonamideYield 90.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 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 (0.061 g, 0.11 mmol) in DCM (2 mL) at room temperature was added trifluoroacetic acid (2.0 mL). The reaction mixture was stirred at room temperature for 30 min and concentrated under reduced pressure. The residue was partitioned between saturated NaHCO3 and EtOAc. 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 (30% to 70% EtOAc in heptane) to give the title compound (0.045 g, 0.10 mmol, 90% yield) as a white solid. MS m/z=446.9 [M+H]+. Calculated for C17H14ClF3N4O3S 446.0. 1H NMR (400 MHz, CDCl3) δ 0.80-0.90 (m, 1H), 1.33 (t, J=6.85 Hz, 1H), 1.69-1.78 (m, 2H), 3.65-3.70 (m, 1H), 5.70 (s br, 2H), 6.06 (t, J=56.10 Hz, 1H), 6.95 (dd, J=6.75, 2.64 Hz, 1H), 7.06 (dd, J=11.44, 8.71 Hz, 1H), 7.45 (ddd, J=8.56, 4.25, 2.84 Hz, 1H), 7.72 (s, 2H), 8.33 (s, 1H).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was partitioned between saturated NaHCO3 and EtOAc
  3. extractionThe aqueous phase was extracted with EtOAc (2×)
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by flash column chromatography on silica gel (30% to 70% EtOAc in heptane)

Sources & evidence

ORD record
ord-c98ef18ff8124ff3bc54657b5119400c
Source dataset
uspto-grants-2015_07
Patent number
US09085576B2

Reaction notes

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