4-tert-Butylbenzoic acid → N-[2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethyl]-4-tert-butyl-benzamide

HRID 430815Notes

Reaction equation

HRID 430815 reaction equation
[C:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[NH2:23][CH:24]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[CH:35][CH:34]=1)[C:25]([NH:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26]>CN(C=O)C>[CH2:40]([O:39][C:36]1[CH:37]=[CH:38][C:33]([CH2:32][CH:24]([NH:23][C:9](=[O:11])[C:8]2[CH:7]=[CH:6][C:5]([C:1]([CH3:2])([CH3:3])[CH3:4])=[CH:13][CH:12]=2)[C:25](=[O:26])[NH:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[CH:34][CH:35]=1)[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

5

Reactant 3

HCID 74034-tert-Butylbenzoic acidHCID 81531DiisopropylethylamineHCID 222559212-amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide

Product 1

HCID 18352025N-[2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethyl]-4-tert-butyl-benzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 0.589 g (3.026 mmol) 4-tert-butylbenzoic acid (Aldrich, Milwaukee Wis.) 1.06 mL (6.5 mmol) N,N-diisopropylethylamine, and 1.15 g (3.026 mmol) O-Benzotriazol-1-yl-N,N,N′,N′-bis(tetramethylene)-uronium hexafluorophosphate in 6 mL dry DMF was stirred in an ice bath for 35 minutes, when 1.00 g (3.026 mmol) of 2-Amino-3-(4-benzyloxy-phenyl)-N-tert-butyl-propionamide (Example 1, Step B) was added. The resulting solution was warmed to 25° C. and stirred for 60 minutes. The mixture was poured into 20 mL diethyl and washed sequentially with 25 mL each of saturated aqueous sodium bicarbonate solution and twice with brine. The mixture was then dried over anhydrous sodium sulfate and concentrated at reduced pressure giving a pale amber solid that was purified by column chromatography on silica gel with 30% ethyl acetate in hexane to give N-[2-(4-benzyloxy-phenyl)-1-tert-butylcarbamoyl-ethyl]-4-tert-butyl-benzamide as a white solid; mp 124-131° C.

Workup

  1. additionThe mixture was poured into 20 mL diethyl
  2. washwashed sequentially with 25 mL each of saturated aqueous sodium bicarbonate solution and twice with brine
  3. dry with materialThe mixture was then dried over anhydrous sodium sulfate
  4. concentrationconcentrated at reduced pressure
  5. customgiving a pale amber solid
  6. customthat was purified by column chromatography on silica gel with 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-1f2627d0a6ee4a678b8bd880b3af32f6
Source dataset
uspto-grants-2001_11
Patent number
US06323243B1

Reaction notes

Loading…