1,1'-Carbonyldiimidazole → Benzyl 2-benzamido-7a-(5-bromo-2-fluoro-phenyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazine-6-carboxylate

HRID 876726Notes

Reaction equation

HRID 876726 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[C:13]([NH:21][C:22]([NH:24][C:25]1([C:42]2[CH:47]=[C:46]([Br:48])[CH:45]=[CH:44][C:43]=2[F:49])[CH:29]([CH2:30]O)[CH2:28][N:27]([C:32]([O:34][CH2:35][C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)=[O:33])[CH2:26]1)=[S:23])(=[O:20])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>O1CCCC1.O>[C:13]([NH:21][C:22]1[S:23][CH2:30][CH:29]2[CH2:28][N:27]([C:32]([O:34][CH2:35][C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[O:33])[CH2:26][C:25]2([C:42]2[CH:47]=[C:46]([Br:48])[CH:45]=[CH:44][C:43]=2[F:49])[N:24]=1)(=[O:20])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

5

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 86762756Benzyl 3-(benzoylcarbamothioylamino)-3-(5-bromo-2-fluoro-phenyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylate

Product 1

HCID 86762759Benzyl 2-benzamido-7a-(5-bromo-2-fluoro-phenyl)-4,4a,5,7-tetrahydropyrrolo[3,4-d][1,3]thiazine-6-carboxylateYield 58.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

1,1′-carbonyldiimidazole (2.87 g, 17.7 mmol) is added to a solution of benzyl 3-(benzoylcarbamothioylamino)-3-(5-bromo-2-fluoro-phenyl)-4-(hydroxymethyl)pyrrolidine-1-carboxylate (5.198 g, 8.86 mmol) in tetrahydrofuran (52 mL). The mixture is stirred for 1.5 hours at room temperature and then the reaction is heated at reflux overnight under nitrogen. The reaction is cooled, diluted with water, and extracted with ethyl acetate (3×). The organic layers are combined, 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 (2.93 g, 58%). ES/MS (m/e): (79Br/81Br). 568/570 (M+H)

Workup

  1. temperaturethe reaction is heated
  2. temperatureat reflux overnight under nitrogen
  3. temperatureThe reaction is cooled
  4. extractionextracted 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-37bc02cdc5044ad2929b61dc91aea914
Source dataset
uspto-grants-2015_03
Patent number
US08987254B2

Reaction notes

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