Tetrahydrofuran → N4-Hydroxy-2-isobutyl-N1-(9-oxo-1,8-diaza-tricyclo(10.6.1.013,18)nonadeca-12(19),13,15,17-tetraen-10-YL)-succinamide

HRID 849729Notes

Reaction equation

HRID 849729 reaction equation
C([O:8][NH:9][C:10](=[O:40])[CH2:11][C@H:12]([C:17](=[O:39])[NH:18][C@H:19]1[CH2:36][C:35]2=[CH:37][N:28]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:34]=32)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][NH:21][C:20]1=[O:38])[CH2:13][CH:14]([CH3:16])[CH3:15])C1C=CC=CC=1.C1COCC1>C(O)C.[Pd]>[OH:8][NH:9][C:10](=[O:40])[CH2:11][C@H:12]([C:17](=[O:39])[NH:18][C@H:19]1[CH2:36][C:35]2=[CH:37][N:28]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:34]=32)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][NH:21][C:20]1=[O:38])[CH2:13][CH:14]([CH3:16])[CH3:15]

Participants

5

Reactant 2

HCID 8028TetrahydrofuranHCID 86752868(3R,10S)-N-benzyloxy-5-methyl-3-(9-oxo-1,8-diazatricyclo[10.6. 1.013,18]nonadeca-12(19),13(18),14,16-tetraen-10-ylcarbamoyl)hexanamide

Product 1

HCID 478379N4-Hydroxy-2-isobutyl-N1-(9-oxo-1,8-diaza-tricyclo(10.6.1.013,18)nonadeca-12(19),13,15,17-tetraen-10-YL)-succinamideYield 92%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

Alternatively, (3R,10S)-N-benzyloxy-5-methyl-3-(9-oxo-1,8-diazatricyclo[10.6. 1.013,18 ]nonadeca-12(19),13(18),14,16-tetraen-10-ylcarbamoyl)hexanamide (1.0 g, 1.83 mmol) was taken up in a solution of 20% THF in ethanol (500 mL) and then Pd on activated charcoal (200 mg) was added portionwise. The resulting slurry was stirred as H2 gas was gently bubbled through the solution. After 4 hours, the reaction mixture was suction filtered through a bed of celite (1.5 cm), and the filtrate was concentrated and then taken up in methanol (30 mL) and filtered through a plug of cotton. Recrystallization from methanol/ethyl acetate/ether/petroleum ether gave (3R,10S)-N-hydroxy-5-methyl-3-(9-oxo-1,8-diaza-tricyclo[10.6.1.013,18 ]nonadeca-12(19),13(18),14,16-tetraen-10-yl-carbamoyl)hexanamide (768 mg, 92%), MS: 455 (M-H)+.

Workup

  1. customwas gently bubbled through the solution
  2. filtrationfiltered through a bed of celite (1.5 cm)
  3. concentrationthe filtrate was concentrated
  4. filtrationfiltered through a plug of cotton
  5. customRecrystallization from methanol/ethyl acetate/ether/petroleum ether

Sources & evidence

ORD record
ord-c8847b739da14f62b170078bea30e936
Source dataset
uspto-grants-2000_01
Patent number
US06013792

Reaction notes

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