4-Methylmorpholine → Benthiavalicarb isopropyl

HRID 1531405Notes

Reaction equation

HRID 1531405 reaction equation
[CH:1]([O:4][C:5]([NH:7][C@H:8]([C:12]([OH:14])=O)[CH:9]([CH3:11])[CH3:10])=[O:6])([CH3:3])[CH3:2].CN1CCOCC1.C(Cl)(=O)OCC(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1.[F:41][C:42]1[CH:53]=[CH:52][C:45]2[N:46]=[C:47]([C@H:49]([NH2:51])[CH3:50])[S:48][C:44]=2[CH:43]=1>C1(C)C=CC=CC=1.O>[F:41][C:42]1[CH:53]=[CH:52][C:45]2[N:46]=[C:47]([C@H:49]([NH:51][C:12]([C@@H:8]([NH:7][C:5](=[O:6])[O:4][CH:1]([CH3:2])[CH3:3])[CH:9]([CH3:10])[CH3:11])=[O:14])[CH3:50])[S:48][C:44]=2[CH:43]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 11063514(2S)-3-methyl-2-(((propan-2-yloxy)carbonyl)amino)butanoic acidHCID 51350477(R)-1-(6-fluoro-2-benzothiazolyl)ethylamine p-toluenesulfonate

Product 1

HCID 53297381Benthiavalicarb isopropylYield 132.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
-5 °C

Procedure

In 500 ml of toluene, 18.9 g (0.093 mol) of N-isopropoxycarbonyl-L-valine was dissolved. The solution was cooled to −5° C. Thereto were dropwise added, at −5° C., 23.0 g (0.233 mol) of N-methylmorpholine and 12.7 g (0.093 mol) of isobutyl chlorocarbonate. Thereto was added, at −5° C., 17.4 g (0.047 mol) of (R)-1-(6-fluoro-2-benzothiazolyl)ethylamine p-toluenesulfonate in one portion. The mixture was stirred at the same temperature for 0.5 hour and then at room temperature for 2 hours. To the reaction mixture was added 300 ml of water. The mixture was heated to 70° C. to dissolve the solid. The toluene layer was separated, washed with hot water, and then cooled, whereby a solid was precipitated. The solid was collected by filtration and dried to obtain 23.7 g (yield: 70%) of isopropyl {(S)-1-[(R)-1-(6-fluorobenzothiazol-2-yl)ethylcarbamoyl]-2-methylpropyl}carbamate. The compound obtained was confirmed for the structure by IR analysis and NMR analysis in comparison with its authentic material and identified.

Workup

  1. additionThereto were dropwise added, at −5° C.
  2. additionThereto was added, at −5° C.
  3. waitat room temperature for 2 hours
  4. temperatureThe mixture was heated to 70° C.
  5. dissolutionto dissolve the solid
  6. customThe toluene layer was separated
  7. washwashed with hot water
  8. temperaturecooled
  9. customwhereby a solid was precipitated
  10. filtrationThe solid was collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-5ef1d0145bbf48adb611dfe184ffa7fe
Source dataset
uspto-grants-2001_03
Patent number
US06197969B1

Reaction notes

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