Triethylamine → (R)-alpha-[(2-t-Butoxycarbonylamino-2-methyl-1-oxopropyl)amino]benzenebutanoic acid benzyl ester

HRID 1911

Reaction equation

HRID 1911 reaction equation
[CH2:1]([O:8][C:9](=[O:20])[C@@H:10]([CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[NH2:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[C:28]([O:32][C:33]([NH:35][C:36]([CH3:41])([C:38](O)=[O:39])[CH3:37])=[O:34])([CH3:31])([CH3:30])[CH3:29].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl>[CH2:1]([O:8][C:9](=[O:20])[C@H:10]([NH:11][C:38](=[O:39])[C:36]([NH:35][C:33]([O:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:34])([CH3:41])[CH3:37])[CH2:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 2733845N-((1,1-dimethylethoxy)carbonyl)-2-methyl-alanineHCID 15630399D-Homophenylalanine Benzyl ester

Product 1

HCID 67665076(R)-alpha-[(2-t-Butoxycarbonylamino-2-methyl-1-oxopropyl)amino]benzenebutanoic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

D-Homophenylalanine benzyl ester (0.87 g; 3.23 mmol), triethylamine (900 ml) and N-(t-butoxycarbonyl)-α-methylalanine (656 mg; 3.23 mmol) were dissolved in dry methylene chloride (6.5 ml) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP-reagent) (1.43 g; 3.23 mmol) was added with stirring in small batches over 10 minutes. The reaction mixture was stirred at room temperature for 2.5 h then quenched by adding saturated brine (25 ml). The two phase system was extracted with methylene chloride (3×25 ml) and the combined methylene chloride extracts dried over magnesium sulfate powder, filtered and evaporated on a rotary evaporator under reduced pressure to give a colorless oil that solidified to an off white solid on standing at room temperature. This solid material was taken up in the minimum volume of methylene chloride and chromatographed on silica gel using an eluant composed of ethyl acetate and hexanes in the ratio 1:3 v/v. The product was isolated after evaporation of the volatiles as a white solid. The yield of the desired product was 1.30 g (88.5%). FAB-MS: -calculated for C26H34N2O5 454.2; found 455.5 (M+1).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 2.5 h
  2. customthen quenched
  3. additionby adding saturated brine (25 ml)
  4. extractionThe two phase system was extracted with methylene chloride (3×25 ml)
  5. dry with materialthe combined methylene chloride extracts dried over magnesium sulfate powder
  6. filtrationfiltered
  7. customevaporated on a rotary evaporator under reduced pressure
  8. customto give a colorless oil that
  9. customon standing at room temperature
  10. customchromatographed on silica gel using an eluant
  11. customThe product was isolated
  12. customafter evaporation of the volatiles as a white solid

Sources & evidence

ORD record
ord-30601e26cfe949648c03f18ace9a74dc
Source dataset
uspto-grants-1998_03
Patent number
US05726319

Linked notes

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