Triethylamine → (R)-alpha-[(3-t-Butoxycarbonylamino-3-methyl-1-oxobutyl)amino]benzenebutanoic acid benzyl ester

HRID 1912

Reaction equation

HRID 1912 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]([CH3:42])([CH3:41])[CH2:37][C:38](O)=[O:39])=[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])[CH2:37][C:36]([NH:35][C:33]([O:32][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:34])([CH3:42])[CH3:41])[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 103760463-((tert-Butoxycarbonyl)amino)-3-methylbutanoic acidHCID 15630399D-Homophenylalanine Benzyl ester

Product 1

HCID 67665936(R)-alpha-[(3-t-Butoxycarbonylamino-3-methyl-1-oxobutyl)amino]benzenebutanoic acid benzyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

D-Homophenylalanine benzyl ester (725 mg; 3.23 mmol) whose preparation was described in Example 7 Step B, triethylamine (750 ml; 5,38 mmol) and 3-t-butoxycarbonylamino-3-methylbutanoic acid (585 mg; 2.69 mmol) were dissolved in dry methylene chloride (10 ml) and BOP (1.19 g, 2.69 mmol) was added with stirring in small batches to give a slightly cloudy solution. The reaction mixture was stirred at room temperature for 24 h then quenched by adding saturated brine (10 ml). The two phase system was extracted with methylene chloride (2×25 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 cloudy, colorless oil. This 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 1:1 v/v. The product was isolated after evaporation of the volatiles as a clear oil. The yield was 710 mg (88.5%). FAB-MS: -calculated for C27H36N2 O5 468.3; found 469.6 (M+1).

Workup

  1. customto give a slightly cloudy solution
  2. stirringThe reaction mixture was stirred at room temperature for 24 h
  3. customthen quenched
  4. additionby adding saturated brine (10 ml)
  5. extractionThe two phase system was extracted with methylene chloride (2×25 ml)
  6. dry with materialthe combined methylene chloride extracts dried over magnesium sulfate powder
  7. filtrationfiltered
  8. customevaporated on a rotary evaporator under reduced pressure
  9. customto give a cloudy, colorless oil
  10. customchromatographed on silica gel using an eluant
  11. customThe product was isolated
  12. customafter evaporation of the volatiles as a clear oil

Sources & evidence

ORD record
ord-a50f7cac2645481a8747ad859fb15edc
Source dataset
uspto-grants-1998_03
Patent number
US05726319

Linked notes

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