4-Methylmorpholine → (2S)-N-[[1-(S-Benzoyl-3-mercaptopropanoyl)-5-(2-hydroxyphenyl)-2-pyrrolidinyl]carbonyl]phenylalanine t-butyl ester

HRID 2295519Notes

Reaction equation

HRID 2295519 reaction equation
[C:1]([S:9][CH2:10][CH2:11][C:12]([N:14]1[CH:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[OH:25])[CH2:17][CH2:16][CH:15]1[C:26]([OH:28])=O)=[O:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.Cl.[C:37]([O:41][C:42](=[O:52])[C@H:43]([CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[NH2:44])([CH3:40])([CH3:39])[CH3:38].C(N(CC)CC)C>C1COCC1.C(Cl)(=O)OCC(C)C>[C:37]([O:41][C:42](=[O:52])[C@H:43]([CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[NH:44][C:26]([C@@H:15]1[CH2:16][CH2:17][CH:18]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[OH:25])[N:14]1[C:12](=[O:13])[CH2:11][CH2:10][S:9][C:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:28])([CH3:40])([CH3:38])[CH3:39]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 8471TriethylamineHCID 11459563L-Phenylalanine, 1,1-dimethylethyl ester, hydrochloride (1:1)HCID 128784451-(S-benzoyl-3-mercaptopropanoyl)-5-(2-hydroxyphenyl)-2-pyrrolidinecarboxylic acid

Product 1

HCID 86739178(2S)-N-[[1-(S-Benzoyl-3-mercaptopropanoyl)-5-(2-hydroxyphenyl)-2-pyrrolidinyl]carbonyl]phenylalanine t-butyl esterYield 83.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 62365Isobutyl chloroformateSolvent

Procedure

To the solution of 1.43 g of 1-(S-benzoyl-3-mercaptopropanoyl)-5-(2-hydroxyphenyl)-2-pyrrolidinecarboxylic acid (mp 89°-92° C. (dec.); [α]D25 +47.4° (c=1.0, methanol)) and 0.3 g of N-methylmorpholine dissolved in 30 ml of dry THF 0.41 g of isobutyl chlorocarbonate is added at a temperature of -15° to -10° C. After stirring it for 30 minutes, the solution of 0.77 g of L-phenylalanine t-butyl ester hydrochloride and 0.3 g of triethylamine dissolved in 10 ml of aqueous THF is added to it. After stirring the mixture under ice-cooling for 30 minutes and at room temperature for an additional 30 minutes, and then removing THF in vacuo, the mixture is extracted with ethyl acetate. The organic layer is washed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution, in order, dried over anhydrous magnesium sulfate, and concentrated in vacuo. The residue is purified by silica gel column chromatography to give 1.5 g (83%) of the titled compound.

Workup

  1. additionis added at a temperature of -15° to -10° C
  2. additionis added to it
  3. stirringAfter stirring the mixture under ice-
  4. extractionremoving THF in vacuo, the mixture is extracted with ethyl acetate
  5. washThe organic layer is washed with saturated aqueous sodium bicarbonate solution, water and saturated aqueous sodium chloride solution, in order
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-9de989d27ce3441c9e301d88e3d8ac6b
Source dataset
uspto-grants-1984_01
Patent number
US04425333

Reaction notes

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