Triethylamine → N-[N-[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]-N-(2,2,2-trichloroethoxycarbonyl)-L-alanyl]-4-hydroxy-L-proline ethyl ester

HRID 1583932Notes

Reaction equation

HRID 1583932 reaction equation
[CH2:1]([O:3][C:4]([C@@H:6]([N:15]([C:21]([O:23][CH2:24][C:25]([Cl:28])([Cl:27])[Cl:26])=[O:22])[C@H:16]([C:18](O)=[O:19])[CH3:17])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:2].C(Cl)(=O)C(Cl)=O.Cl.[CH2:36]([O:38][C:39](=[O:46])[C@@H:40]1[CH2:44][CH:43]([OH:45])[CH2:42][NH:41]1)[CH3:37].C(N(CC)CC)C>C(Cl)Cl.CN(C)C=O>[CH2:36]([O:38][C:39](=[O:46])[C@@H:40]1[CH2:44][CH:43]([OH:45])[CH2:42][N:41]1[C:18](=[O:19])[C@H:16]([CH3:17])[N:15]([C@H:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:21]([O:23][CH2:24][C:25]([Cl:27])([Cl:28])[Cl:26])=[O:22])[CH3:37]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 127093054hydroxy-L-proline ethyl ester hydrochlorideHCID 13376527N-((1S)-1-ethoxycarbonyl-3-phenylpropyl)-N-(2,2,2-trichloroethoxycarbonyl)alanine

Product 1

HCID 13690737N-[N-[(1S)-1-(Ethoxycarbonyl)-3-phenylpropyl]-N-(2,2,2-trichloroethoxycarbonyl)-L-alanyl]-4-hydroxy-L-proline ethyl esterYield 41%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To N-[(1S)-1-(ethoxycarbonyl)-3-phenylpropyl]-N-(2,2,2-trichloroethoxycarbonyl)-L-alanine (5.94 g, 13.07 mmol) in 50 ml methylene chloride, under N2, was added oxalyl chloride (5.70 ml, 65.33 mmol) and then N,N-dimethylformamide (20 uL). The solution was stirred 3.5 hours and concentrated in vacuo. The residue was diluted with 30 ml methylene chloride and cooled with an ice bath while under N2. To this solution was added portionwise a mixture of 4-hydroxy-L-proline ethyl ester hydrochloride (1.96 g, 10.05 mmol) and triethylamine (6.99 ml, 50.25 mmol) in 40 ml methylene chloride. After the addition was complete the solution was slowly warmed to room temperature, stirred 18 hours and concentrated in vacuo. The residue was dissolved in ether and washed with water, 10% HCl, 1N NaOH, and brine, and dried (MgSO4) and concentrated in vacuo. Chromatography of the residue on HPLC, using 50% ethyl acetate in hexanes as eluents, provided 2.44 g (41%) of the oily product.

Workup

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted with 30 ml methylene chloride
  3. temperaturecooled with an ice bath while under N2
  4. additionTo this solution was added portionwise
  5. additionAfter the addition
  6. stirringstirred 18 hours
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue was dissolved in ether
  9. washwashed with water, 10% HCl, 1N NaOH, and brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3037838b6b8a4a1ab40048ce35c3e6e0
Source dataset
uspto-grants-1985_11
Patent number
US04555508

Reaction notes

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