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Benzyl 1-(benzoylcarbamothioyl)-6a-(5-bromo-2-fluoro-phenyl)-3,3a,4,6-tetrahydropyrrolo[3,4-c]isoxazole-5-carboxylate → Benzyl 3-(benzoylcarbamothioylamino)-3-(5-bromo-2-fluoro-phenyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylate

HRID 77573
Notes
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Reaction equation

HRID 77573 reaction equation
[C:1]([NH:9][C:10]([N:12]1[C:16]2([C:30]3[CH:35]=[C:34]([Br:36])[CH:33]=[CH:32][C:31]=3[F:37])[CH2:17][N:18]([C:20]([O:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[CH2:19][CH:15]2[CH2:14][O:13]1)=[S:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)(=O)C.C(OCC)(=O)C.[Zn]>[C:1]([NH:9][C:10]([NH:12][C:16]1([C:30]2[CH:35]=[C:34]([Br:36])[CH:33]=[CH:32][C:31]=2[F:37])[CH:15]([CH2:14][OH:13])[CH2:19][N:18]([C:20]([O:22][CH2:23][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)=[O:21])[CH2:17]1)=[S:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 1

HCID 86762753Benzyl 1-(benzoylcarbamothioyl)-6a-(5-bromo-2-fluoro-phenyl)-3,3a,4,6-tetrahydropyrrolo[3,4-c]isoxazole-5-carboxylate

Product 1

HCID 86762756Benzyl 3-(benzoylcarbamothioylamino)-3-(5-bromo-2-fluoro-phenyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylateYield 86%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent
HCID 8857
Ethyl Acetate
Solvent

Procedure

A mixture of benzyl 1-(benzoylcarbamothioyl)-6a-(5-bromo-2-fluoro-phenyl)-3,3a,4,6-tetrahydropyrrolo[3,4-c]isoxazole-5-carboxylate (6.05 g 10.4 mmol) and zinc (dust, <10 micron) (6.77 g, 103.5 mmol) is stirred in acetic acid (52 mL) at room temperature overnight under nitrogen. The reaction is diluted with ethyl acetate and filtered through diatomaceous earth. The solvent is removed in vacuo and the residue is diluted with ethyl acetate, water and saturated aqueous sodium bicarbonate. The mixture is extracted with ethyl acetate (3×), the combined organic layers are combined and dried over sodium sulfate, filtered and the solvent removed in vacuo. The crude product is purified over silica gel with a 30 minute 5% to 100% EtOAc in hexanes gradient to give the title compound (5.222 g, 86%). ES/MS (m/e): (79Br/81Br) 586/588 (M+H).

Workup

  1. filtrationfiltered through diatomaceous earth
  2. customThe solvent is removed in vacuo
  3. additionthe residue is diluted with ethyl acetate, water and saturated aqueous sodium bicarbonate
  4. extractionThe mixture is extracted with ethyl acetate (3×)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent removed in vacuo
  8. customThe crude product is purified over silica gel with a 30 minute 5% to 100% EtOAc in hexanes gradient

Sources & evidence

ORD record
ord-4f4da25953a04484b00b4d56903b7f91
Source dataset
uspto-grants-2014_09
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08841293B1

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes