Acetic Acid → 9-Fluoro-5-oxo-2,3,4,5-tetrahydrobenzo[e][1,4]diazepine-1-carboxylic acid tert-butyl ester

HRID 558983Notes

Reaction equation

HRID 558983 reaction equation
C(OC([NH:11][CH2:12][CH2:13][N:14]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C:15]1[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:16]=1[C:17](O)=[O:18])=O)C1C=CC=CC=1.C(O)(=O)C>CO.[Pd]>[C:28]([O:27][C:25]([N:14]1[C:15]2[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:16]=2[C:17](=[O:18])[NH:11][CH2:12][CH2:13]1)=[O:26])([CH3:31])([CH3:30])[CH3:29]

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 670000432-[(2-Benzyloxycarbonylaminoethyl)-tert-butoxycarbonylamino]-3-fluorobenzoic acid

Product 1

HCID 670000169-Fluoro-5-oxo-2,3,4,5-tetrahydrobenzo[e][1,4]diazepine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

A solution of 2-[(2-benzyloxycarbonylaminoethyl)-tert-butoxycarbonylamino]-3-fluorobenzoic acid from Example 20B (390 mg, 0.87 mmol), 10% palladium/carbon (˜100 mg) and acetic acid (1.0 ml) in methanol (25 ml) was hydrogenated at atmospheric pressure for 1.5 h. The mixture was filtered, evaporated in vacuo and azeotroped with toluene. The residue was taken up in a mixture of IPA and acetic acid (90:10, 35 ml) and heated at reflux for 4 h. The mixture was cooled, evaporated in vacuo and azeotroped with toluene to give a white solid; yield 250 mg, 100%.

Workup

  1. filtrationThe mixture was filtered
  2. customevaporated in vacuo
  3. customazeotroped with toluene
  4. additionThe residue was taken up in a mixture of IPA and acetic acid (90:10, 35 ml)
  5. temperatureheated
  6. temperatureat reflux for 4 h
  7. temperatureThe mixture was cooled
  8. customevaporated in vacuo
  9. customazeotroped with toluene
  10. customto give a white solid

Sources & evidence

ORD record
ord-24c63e0341914c05ad86e49d3b5d1f40
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

Loading…