Dicyclohexylcarbodiimide → (3R)-4-(4-toluenesulfonyl)thiomorpholine-3-carboxylic acid [3-(pyridin-3-yl)]-propyl ester

HRID 968523Notes

Reaction equation

HRID 968523 reaction equation
[C:1]1([CH3:19])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[CH2:15][CH2:14][S:13][CH2:12][C@H:11]2[C:16]([OH:18])=[O:17])(=[O:9])=[O:8])=[CH:3][CH:2]=1.[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][CH2:27][CH2:28]O)[CH:21]=1.C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH2:26][CH2:27][CH2:28][O:17][C:16]([C@@H:11]2[CH2:12][S:13][CH2:14][CH2:15][N:10]2[S:7]([C:4]2[CH:3]=[CH:2][C:1]([CH3:19])=[CH:6][CH:5]=2)(=[O:9])=[O:8])=[O:18])[CH:21]=1

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 178613-PyridinepropanolHCID 69415969(3R)-4-(4-toluenesulfonyl)thiomorpholine-3-carboxylic acid

Product 1

HCID 86598599(3R)-4-(4-toluenesulfonyl)thiomorpholine-3-carboxylic acid [3-(pyridin-3-yl)]-propyl esterYield 92.7%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

0.301 g (1 mmol) of (3R)-4-(4-toluenesulfonyl)thiomorpholine-3-carboxylic acid, 0.206 g (1.5 mmol) of 3-(pyridin-3-yl)-propanol, 0.088 g (0.33 mmol) of CAS, 0.227 g (1.2 mmol) of DCC and 0.04 g (0.33 mmol) of DMAP were dissolved in 15 mL of CH2Cl2. The mixture was stirred for 24 h at room temperature. The solid was filtrated and the solvent was evaporated. The residual was dissolved in a suitable amount of ethyl acetate (20 ml) and then the mixture was filtered to remove insoluble substance. The ethyl acetate was added to 60 ml and then the liquid was washed with 10% NaHCO3 solution, saturated NaCl solution and dried over Na2SO4. After the drying agent was removed and part of ethyl acetate was evaporated, the crude product was purified by flash column chromatography (eluent: ethyl acetate:cyclohexane=1:1) to obtain the product as a oil (0.39 g).

Workup

  1. filtrationThe solid was filtrated
  2. customthe solvent was evaporated
  3. dissolutionThe residual was dissolved in a suitable amount of ethyl acetate (20 ml)
  4. filtrationthe mixture was filtered
  5. customto remove insoluble substance
  6. additionThe ethyl acetate was added to 60 ml
  7. washthe liquid was washed with 10% NaHCO3 solution, saturated NaCl solution
  8. dry with materialdried over Na2SO4
  9. customAfter the drying agent was removed
  10. custompart of ethyl acetate was evaporated
  11. customthe crude product was purified by flash column chromatography (eluent: ethyl acetate:cyclohexane=1:1)

Sources & evidence

ORD record
ord-f031494d917641188ad9f9b37003c470
Source dataset
uspto-grants-2007_12
Patent number
US07304057B2

Reaction notes

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