4-(Hydroxymethyl)benzoic acid → N-(2-t-Butoxycarbonylaminophenyl)-4-hydroxymethylbenzamide

HRID 658031Notes

Reaction equation

HRID 658031 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([O:29][C:30](=[O:39])[NH:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[NH2:38])([CH3:28])([CH3:27])[CH3:26].[OH:40][CH2:41][C:42]1[CH:50]=[CH:49][C:45]([C:46](O)=[O:47])=[CH:44][CH:43]=1.C(N(CC)C(C)C)(C)C>CN(C=O)C.O>[C:25]([O:29][C:30]([NH:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[NH:38][C:41](=[O:40])[C:42]1[CH:50]=[CH:49][C:45]([CH2:46][OH:47])=[CH:44][CH:43]=1)=[O:39])([CH3:28])([CH3:26])[CH3:27]

Participants

7

Reactant 4

HCID 763604-(Hydroxymethyl)benzoic acidHCID 81531DiisopropylethylamineHCID 676311N-(tert-Butoxycarbonyl)-1,2-phenylenediamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 1

HCID 20786191N-(2-t-Butoxycarbonylaminophenyl)-4-hydroxymethylbenzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

HATU (17 g, 45 mmol) was added to a solution of 2-aminophenylcarbamic acid t-butyl ester (Reference Compound No. 1-1, 8.3 g, 40 mmol), 4-hydroxymethylbenzoic acid (6.2 g, 41 mmol) and N,N-diisopropylethylamine (21 mL, 120 mmol) in anhydrous DMF (200 mL), and then the mixture was stirred at room temperature for 16 hours. Water (500 mL) was added thereto, the whole was extracted with ethyl acetate (500 mL) twice, and then the organic layer was washed with brine (500 mL) twice. The organic layer was dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform-methanol) to give 1.7 g of the title reference compound as a pale yellow solid. (Yield 42%)

Workup

  1. extractionthe whole was extracted with ethyl acetate (500 mL) twice
  2. washthe organic layer was washed with brine (500 mL) twice
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (chloroform-methanol)
  6. customto give 1.7 g of the title reference compound as a pale yellow solid

Sources & evidence

ORD record
ord-471845a5981949bebcf4609533e4ae3e
Source dataset
uspto-grants-2011_12
Patent number
US08076332B2

Reaction notes

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