Acetic Acid → tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate

HRID 923537Notes

Reaction equation

HRID 923537 reaction equation
C(OC1C=CC(C([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][N:23]([CH2:44][C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[C:24](=[O:43])[C:25]3[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:42])[CH2:33][C:34]4[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=4)=[CH:27][CH:26]=3)=[CH:18][CH:17]=2)=O)=CC=1)CCCCCC.[OH-].[Na+].CO.CC(O)=O>C1COCC1>[OH:15][C:16]1[CH:17]=[CH:18][C:19]([CH2:22][N:23]([CH2:44][C:45]([O:47][C:48]([CH3:49])([CH3:50])[CH3:51])=[O:46])[C:24](=[O:43])[C:25]2[CH:30]=[CH:29][C:28]([NH:31][C:32](=[O:42])[CH2:33][C:34]3[CH:39]=[CH:38][C:37]([O:40][CH3:41])=[CH:36][CH:35]=3)=[CH:27][CH:26]=2)=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 892531624-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)methyl)phenyl 4-(heptyloxy)benzoate

Product 1

HCID 71076654tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetateYield 56%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Prepared using General Procedure 9: To a stirring solution of 4-((N-(2-(tert-butoxy)-2-oxoethyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)methyl)phenyl 4-(heptyloxy)benzoate INT-5 (6.38 g, 8.83 mmol) in THF (50 mL) was added 1N NaOH (16 mL). The reaction was stirred for 1 h. MeOH (10 mL) was added causing the turbid reaction mixture to clarify. The reaction was stirred for 3 h then neutralized with AcOH. The crude mixture was concentrated then diluted with DCM (60 mL) and washed with brine (30 mL). The organic layer was concentrated and purified by chromatography (EA/hexanes) to afford 2.5 g (56%) of tert-butyl 2-(N-(4-hydroxybenzyl)-4-(2-(4-methoxyphenyl)acetamido)benzamido)acetate INT-7. LCMS-ESI (m/z) calculated for C29H32N2O6: 504; found 503 [M−H]−, tR=2.09 min. (Method 3). 1H NMR (400 MHz, DMSO) δ 10.22 (s, 1H), 9.41-9.29 (m, 1H), 7.69-7.59 (d, J=8.1 Hz, 2H), 7.42-7.20 (m, 4H), 7.19-6.96 (m, 2H), 6.91-6.84 (m, 2H), 6.76-6.68 (m, 2H), 4.58-4.35 (m, 2H), 3.90-3.76 (m, 2H), 3.71 (s, 3H), 3.57 (s, 2H), 1.49-1.21 (m, 9H).

Workup

  1. customPrepared
  2. customthe turbid reaction mixture
  3. stirringThe reaction was stirred for 3 h
  4. concentrationThe crude mixture was concentrated
  5. additionthen diluted with DCM (60 mL)
  6. washwashed with brine (30 mL)
  7. concentrationThe organic layer was concentrated
  8. custompurified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-67e2e1090da14b0a8b32c95bbae72774
Source dataset
uspto-grants-2016_03
Patent number
US09278910B2

Reaction notes

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