Tetrahydrofuran → HCID 14129893, compound

HRID 1252162Notes

Reaction equation

HRID 1252162 reaction equation
C(C[CH2:5][N:6]([CH3:24])[C:7]([N:9]1[CH2:23][CH2:22][CH2:21][C@H:10]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:8])(O)=O.O1CCCC1.C(Cl)(=O)C(Cl)=O.[C:36]1([C:42]2[O:43][C:44](=[O:51])[CH:45]([CH2:47][CH2:48][CH2:49][CH3:50])[N:46]=2)[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CN(C)C=O.C(N(CC)CC)C>[C:42]([NH:46][CH:45]([CH2:47][CH2:48][CH2:49][CH3:50])[C:44](=[O:51])[CH2:5][N:6]([CH3:24])[C:7]([N:9]1[CH2:23][CH2:22][CH2:21][C@H:10]1[C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])=[O:8])(=[O:43])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 65578Oxalyl chlorideHCID 13657320HCID 13657320, compoundHCID 141299024-Butyl-2-phenyl-1,3-oxazol-5(4H)-one

Product 1

HCID 14129893HCID 14129893, compoundYield 15.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8471TriethylamineSolvent

Procedure

1-[[(2-Carboxyethyl)methylamino]carbonyl]-L-proline, phenylmethyl ester (4.8 g., 15 mmole) is taken into 50 ml. of dry tetrahydrofuran with stirring in an ice bath. To this is added dropwise oxalyl chloride (1.58 ml., 18 mmole) followed by 4 drops of dimethylformamide. After 20 minutes the bath is removed and the reaction is run for one hour at room temperature before concentrating to dryness. This material is taken into 30 ml. of tetrahydrofuran, chilled and added dropwise to 2-phenyl-4-butyl-5(4H)-oxazolone (3.42 g., 15.75 mmole) in 24 ml. of tetrahydrofuran while stirring in an ice bath. Triethylamine (2.55 ml.) is added. After 5 minutes the bath is removed and the reaction is run overnight at room temperature. The triethylamine hydrochlorice salt is filtered off, the filtrate is concentrated to dryness, taken into 16 ml. of pyridine, 50 mg. of 4-dimethylamino pyridine is added, and the mixture is stirred for 3 hours. Acetic acid (16 ml.) is added and the mixture is heated at 100° for 45 minutes. The mixture is concentrated to dryness, taken into ethyl acetate and washed neutral with saturated sodium bicarbonate and dilute hydrochloric acid to give 4.7 g. of product. Purification on silica gel in benzene:ethyl acetate (1:2) yields 1.14 g of (±)-1-[[[3-(benzoylamino)-2-oxoheptyl]methylamino]carbonyl]-L-proline, phenylmethyl ester.

Workup

  1. customAfter 20 minutes the bath is removed
  2. concentrationbefore concentrating to dryness
  3. temperatureof tetrahydrofuran, chilled
  4. customAfter 5 minutes the bath is removed
  5. waitthe reaction is run overnight at room temperature
  6. filtrationThe triethylamine hydrochlorice salt is filtered off
  7. concentrationthe filtrate is concentrated to dryness
  8. additionof 4-dimethylamino pyridine is added
  9. additionAcetic acid (16 ml.) is added
  10. temperaturethe mixture is heated at 100° for 45 minutes
  11. concentrationThe mixture is concentrated to dryness
  12. washwashed neutral with saturated sodium bicarbonate and dilute hydrochloric acid
  13. customto give 4.7 g
  14. customPurification on silica gel in benzene:ethyl acetate (1:2)

Sources & evidence

ORD record
ord-1497221ef6504bc39b3ec56aeb80dc01
Source dataset
uspto-grants-1988_05
Patent number
US04742067

Reaction notes

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