4-{[(Tert-butoxy)carbonyl]amino}benzoic acid → tert-butyl 2-(N-(4-bromobenzyl)-4-((tert-butoxycarbonyl)amino)benzamido)acetate

HRID 923603Notes

Reaction equation

HRID 923603 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Br:18][C:19]1[CH:34]=[CH:33][C:22]([CH2:23][NH:24][CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[CH:21][CH:20]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.CC(=O)OCC>[Br:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:23][N:24]([CH2:25][C:26]([O:28][C:29]([CH3:30])([CH3:31])[CH3:32])=[O:27])[C:13](=[O:15])[C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[CH:17][CH:16]=2)=[CH:33][CH:34]=1

Participants

6

Reactant 3

HCID 27559314-{[(Tert-butoxy)carbonyl]amino}benzoic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 60824820Tert-butyl 2-{[(4-bromophenyl)methyl]amino}acetate

Product 1

HCID 71076642tert-butyl 2-(N-(4-bromobenzyl)-4-((tert-butoxycarbonyl)amino)benzamido)acetateYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Prepared using General Procedure 6: To a stirred solution of 4-((tert-butoxycarbonyl)amino)benzoic acid (2.0 g, 8.43 mmol), tert-butyl 2-((4-bromobenzyl)amino)acetate INT-60 (2.53 g, 8.43 mmol) and TEA (1.76 mL, 12.6 mmol) in DMF (15 mL) was added HATU (3.53 g, 9.27 mmol) at room temperature. After stirring at room temperature for 2 h the reaction mixture was diluted with EA (150 mL) and washed with brine (200 mL). The organics were concentrated in vacuo and the residue was purified by chromatography (EA/hexanes) to afford 3.97 g (91%) of tert-butyl 2-(N-(4-bromobenzyl)-4-((tert-butoxycarbonyl)amino)benzamido)acetate INT-61 as a viscous oil. LCMS-ESI (m/z) calculated for C25H31BrN2O5: 519; found: 517/519 [M−H]−, tR=2.68 min (Method 10).

Workup

  1. customPrepared
  2. washwashed with brine (200 mL)
  3. concentrationThe organics were concentrated in vacuo
  4. customthe residue was purified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-dab248a5072e4e7fa958094ac2d1ed21
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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