Sodium Iodide → 2-[(2-Benzyloxycarbonylaminoethyl)-tert-butoxycarbonylamino]-3-fluorobenzoic acid

HRID 558982Notes

Reaction equation

HRID 558982 reaction equation
[H-].[Na+].C[O:4][C:5](=[O:21])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([F:12])[C:7]=1[NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].[CH2:22]([O:29][C:30](=[O:35])[NH:31][CH2:32][CH2:33]Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[I-].[Na+]>CN(C=O)C>[CH2:22]([O:29][C:30]([NH:31][CH2:32][CH2:33][N:13]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:7]1[C:8]([F:12])=[CH:9][CH:10]=[CH:11][C:6]=1[C:5]([OH:4])=[O:21])=[O:35])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 278694benzyl N-(2-bromoethyl)carbamateHCID 67000076HCID 67000076, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60%, 120 mg, 3.0 mmol) was added to a solution of 2-tert-butoxycarbonylamino-3-fluorobenzoic acid methyl ester from Example 20A (750 mg, 2.8 mmol) in DMF (8.0 ml) while cooling in an ice/water bath. The mixture was allowed to warm to room temperature and stirred for 30 min. (2-bromoethyl)carbamic acid benzyl ester (360 mg, 2.8 mmol) and sodium iodide (420 mg, 2.8 mmol) were added and the mixture was heated at 65° C. for 18 h. The mixture was cooled and evaporated in vacuo. The residue was partitioned between EtOAc and brine and the organic layer was dried and evaporated in vacuo. The residue was purified by flash chromatography on silica (EtOAc:pet. ether 30:70) to give a colourless gum; yield 340 mg, 27%.

Workup

  1. temperaturewhile cooling in an ice/water bath
  2. additionwere added
  3. temperaturethe mixture was heated at 65° C. for 18 h
  4. temperatureThe mixture was cooled
  5. customevaporated in vacuo
  6. customThe residue was partitioned between EtOAc and brine
  7. customthe organic layer was dried
  8. customevaporated in vacuo
  9. customThe residue was purified by flash chromatography on silica (EtOAc:pet. ether 30:70)
  10. customto give a colourless gum

Sources & evidence

ORD record
ord-e14fb0a72cd5462aa7755bb12009961b
Source dataset
uspto-grants-2011_11
Patent number
US08063038B2

Reaction notes

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