PyBOP → tert-butyl 2-(N-(4-bromobenzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate

HRID 923626Notes

Reaction equation

HRID 923626 reaction equation
[Br:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][NH:7][CH2:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[CH:4][CH:3]=1.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C:27]([NH:29][C:30]2[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][CH:31]=2)=[O:28])=[C:22]([C:39]([F:42])([F:41])[F:40])[CH:21]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C.CC(=O)OCC>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][N:7]([CH2:8][C:9]([O:11][C:12]([CH3:13])([CH3:14])[CH3:15])=[O:10])[C:34](=[O:35])[C:33]2[CH:37]=[CH:38][C:30]([NH:29][C:27](=[O:28])[CH2:26][C:23]3[CH:24]=[CH:25][C:20]([O:19][CH3:18])=[CH:21][C:22]=3[C:39]([F:42])([F:40])[F:41])=[CH:31][CH:32]=2)=[CH:16][CH:17]=1

Participants

6

Reactant 3

HCID 2724699PyBOPHCID 60824820Tert-butyl 2-{[(4-bromophenyl)methyl]amino}acetateHCID 710767434-(2-(4-Methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid

Product 1

HCID 71076776tert-butyl 2-(N-(4-bromobenzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetateYield 91%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Prepared from INT-60 and INT-18. To a stirring solution of tert-butyl 2-((4-bromobenzyl)amino)acetate INT-60 (2.7 g, 8.99 mmol), 4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzoic acid INT-18 (3.18 g, 8.99 mmol) and TEA (2.507 mL, 17.99 mmol) in DMF was added PyBOP (4.91 g, 9.44 mmol) at room temperature. After 2 h the reaction mixture was diluted with EA (200 mL) and washed with 1 M HCl (100 mL), NaHCO3 (200 mL) and brine (200 mL). The organics were dried over MgSO4, pre-absorbed onto silica gel and purified by chromatography (EA/hexanes) to afford 5.2 g (91%) of tert-butyl 2-(N-(4-bromobenzyl)-4-(2-(4-methoxy-2-(trifluoromethyl)phenyl)acetamido)benzamido)acetate INT-81 as a white foamy solid. LCMS-ESI (m/z) calculated for C30H30BrF3N2O5: 635; found 579/581 [M-tBu+H]+, tR=2.83 min (Method 10).

Workup

  1. customPrepared from INT-60 and INT-18
  2. washwashed with 1 M HCl (100 mL), NaHCO3 (200 mL) and brine (200 mL)
  3. dry with materialThe organics were dried over MgSO4
  4. custompre-absorbed onto silica gel
  5. custompurified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-8ab0832dfff54048879c61509cb9368a
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

Loading…