Dicyclohexylcarbodiimide → (1R,4R)-3-Benzoyl-4-[(R)-alpha-methyl-p-hydroxybenzylcarbamoyl]-1-oxothiazolidine

HRID 1200159Notes

Reaction equation

HRID 1200159 reaction equation
[CH3:1][C@@H:2]([NH2:10])[C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1.O.ON1C2C=CC=CC=2N=N1.C1(N=C=NC2CCCCC2)CCCCC1.[C:37]([N:45]1[C@H:49]([C:50](O)=[O:51])[CH2:48][S@@:47](=[O:53])[CH2:46]1)(=[O:44])[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>CN(C)C=O>[C:37]([N:45]1[C@H:49]([C:50](=[O:51])[NH:10][C@H:2]([CH3:1])[C:3]2[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=2)[CH2:48][S@@:47](=[O:53])[CH2:46]1)(=[O:44])[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 13986800(1R,4R)-3-benzoyl-1-oxo-thiazolidine-4-carboxylic acidHCID 146963084-((1R)-1-Aminoethyl)phenol

Product 1

HCID 14696330(1R,4R)-3-Benzoyl-4-[(R)-alpha-methyl-p-hydroxybenzylcarbamoyl]-1-oxothiazolidineYield 74.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

9.47 g (69.11 mmole) of (R)-α-methyl-p-hydroxybenzylamine (prepared as described in Preparation 13), 10.58 g (69.11 mmole) of N-hydroxybenzotriazole monohydrate and 14.26 g (69.11 mmole) of dicyclohexylcarbodiimide were added in that order to a solution of 17.50 g (69.11 mmole) of (1R,4R)-3-benzoyl-1-oxo-thiazolidine-4-carboxylic acid (prepared as described in Preparation 10) in 100 ml of dimethylformamide cooled at 5° C., and the mixture was stirred at a temperature between 3° and 6° C. for 30 minutes and then at room temperature for a further 4 hours. At the end of this time, the reaction mixture was filtered and the insolubles were washed with 100 ml of hot dimethylformamide. The filtrate and the washings were combined and concentrated by evaporation under reduced pressure to leave crystals. These crystals were recrystallized from methanol to give 19.21 g (74.6%) of the title compound in the form of colorless needles melting at 233°-234° C.

Workup

  1. waitat room temperature for a further 4 hours
  2. filtrationAt the end of this time, the reaction mixture was filtered
  3. washthe insolubles were washed with 100 ml of hot dimethylformamide
  4. concentrationconcentrated by evaporation under reduced pressure
  5. customto leave crystals
  6. customThese crystals were recrystallized from methanol

Sources & evidence

ORD record
ord-c378ca8c01614734af1cb78e95f7eefd
Source dataset
uspto-grants-1990_02
Patent number
US04904680

Reaction notes

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