Stannous chloride dihydrate → HCID 72706949, compound

HRID 59729Notes

Reaction equation

HRID 59729 reaction equation
[Cl:1][C:2]1[CH:3]=[N+:4]([O-:46])[CH:5]=[C:6]([Cl:45])[C:7]=1[CH2:8][C@@H:9]([C:30]1[CH:35]=[CH:34][C:33]([O:36][CH:37]([F:39])[F:38])=[C:32]([O:40][CH2:41][CH:42]2[CH2:44][CH2:43]2)[CH:31]=1)[O:10][C:11]([C:13]1[N:14]([S:18]([C:21]2[CH:26]=[CH:25][C:24]([N+:27]([O-])=O)=[CH:23][CH:22]=2)(=[O:20])=[O:19])[CH:15]=[CH:16][CH:17]=1)=[O:12].O.O.[Sn](Cl)Cl>C1COCC1>[NH2:27][C:24]1[CH:23]=[CH:22][C:21]([S:18]([N:14]2[CH:15]=[CH:16][CH:17]=[C:13]2[C:11]([O:10][C@H:9]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH:37]([F:38])[F:39])=[C:32]([O:40][CH2:41][CH:42]3[CH2:44][CH2:43]3)[CH:31]=2)[CH2:8][C:7]2[C:2]([Cl:1])=[CH:3][N+:4]([O-:46])=[CH:5][C:6]=2[Cl:45])=[O:12])(=[O:20])=[O:19])=[CH:26][CH:25]=1

Participants

4

Reactant 2

HCID 61436Stannous chloride dihydrate2×HCID 86703836(S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(1-(4-nitrophenylsulfonyl)-1H-pyrrole-2-carbonyloxy)-ethyl)pyridine 1-oxide

Product 1

HCID 72706949HCID 72706949, compoundYield 51.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-(1-(4-nitrophenylsulfonyl)-1H-pyrrole-2-carbonyloxy)-ethyl)pyridine 1-oxide (Int. 6) (424 mg, 0.607 mmol) and tin(II) chloride dihydrate (548 mg, 2.428 mmol) in THF (40 ml) was heated at 45° C. for 2 hours. Additional tin(II) chloride dihydrate (1.644 g, 7.284 mmol) was added in 3 portion over 3 hours at 60° C., and the resulting mixture was heated to reflux overnight. The solvent was removed and the mixture was diluted with ethyl acetate; aqueous sat. NaHCO3 was added and the mixture was filtered through a celite pad. The filtered phases were separated and the organic layer was washed with brine and dried over sodium sulfate; the solvent was removed and the crude was purified by flash chromatography on silica gel column (DCM/MeOH=98/2) affording (S)-4-(2-(1-(4-aminophenylsulfonyl)-1H-pyrrole-2-carbonyloxy)-2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)ethyl)-3,5-dichloropyridine 1-oxide (Int. 7) (207 mg, 0.310 mmol, MS/ESI+667.96 [MH]+, [αD]=−61.24, c=1, DCM).

Workup

  1. temperaturethe resulting mixture was heated
  2. temperatureto reflux overnight
  3. customThe solvent was removed
  4. additionthe mixture was diluted with ethyl acetate
  5. additionaqueous sat. NaHCO3 was added
  6. filtrationthe mixture was filtered through a celite pad
  7. customThe filtered phases were separated
  8. washthe organic layer was washed with brine
  9. dry with materialdried over sodium sulfate
  10. customthe solvent was removed
  11. customthe crude was purified by flash chromatography on silica gel column (DCM/MeOH=98/2)

Sources & evidence

ORD record
ord-73c363d06d614eee8b2de7b2d860ed26
Source dataset
uspto-grants-2016_09
Patent number
US09440954B2

Reaction notes

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