Hydrochloric Acid → Benthiavalicarb isopropyl

HRID 1369138Notes

Reaction equation

HRID 1369138 reaction equation
[OH-].[Na+].[NH2:3][C@H:4]([C:8]([OH:10])=O)[CH:5]([CH3:7])[CH3:6].[C:11](Cl)(=[O:16])[O:12][CH:13]([CH3:15])[CH3:14].Cl.[F:19][C:20]1[CH:31]=[CH:30][C:23]2[N:24]=[C:25]([C@H:27]([NH2:29])[CH3:28])[S:26][C:22]=2[CH:21]=1>C1(C)C=CC=CC=1.CNN(CC1C=CC=CC=1)NC.O>[F:19][C:20]1[CH:31]=[CH:30][C:23]2[N:24]=[C:25]([C@H:27]([NH:29][C:8]([C@@H:4]([NH:3][C:11](=[O:16])[O:12][CH:13]([CH3:15])[CH3:14])[CH:5]([CH3:7])[CH3:6])=[O:10])[CH3:28])[S:26][C:22]=2[CH:21]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6287L-ValineHCID 7917Isopropyl chloroformate2×HCID 14798Sodium HydroxideHCID 10921462(R)-1-(6-Fluorobenzo[D]thiazol-2-YL)ethanamine

Product 1

HCID 53297381Benthiavalicarb isopropylYield 92.4%

Reagents, catalysts & solvents 3

HCID 86587301N,N-dimethylaminobenzylamineCatalystHCID 962WaterSolvent2×HCID 1140TolueneSolvent2×

Procedure

16.1 g (0.092 mole) of 23% sodium hydroxide, 10 ml of water and 4.7 g (0.04 mole) of L-valine were placed in a 300-ml reaction flask, and stirred at room temperature for 30 minutes. Thereto was dropwise added 5.9 g.(0.048 mole) of isopropyl chlorocarbonate at room temperature, followed by stirring for 1 hour. The resulting mixture was neutralized with concentrated hydrochloric acid. Thereto were added 50 ml of toluene and 0.06 g (0.0004 mole) of N,N-dimethylaminobenzylamine. Then, 4.7 g (0.038 mole) of isopropyl chlorocarbonate was added dropwise at room temperature, followed by stirring for 1 hour. Thereafter, there was dropwise added a solution of 7.5 g (0.038 mole) of (R)-1-(6-fluorobenzothiazol-2-yl)ethylamine (purity: 98.3%, optical purity: 99.0% ee) dissolved in 50 ml of toluene, produced according to the above Reference Example, followed by stirring at room temperature for 2 hours. 50 ml of water was added; the resulting mixture was heated to 70° C. and subjected to phase separation; the toluene layer was washed with 50 ml of hot water and subjected to solvent removal to obtain 13.4 g (yield: 92.4%) of isopropyl [(S)-1-[(R)-1(6-fluorobenzothiazol-2-yl)ethylcarbamoyl]-2-methylpropyl]carbamate (purity: 96.3%, the proportion of formed intended substance in four diastereomers: 98.5%).

Workup

  1. customat room temperature
  2. stirringby stirring for 1 hour
  3. stirringby stirring for 1 hour
  4. customproduced
  5. stirringby stirring at room temperature for 2 hours
  6. temperaturethe resulting mixture was heated to 70° C.
  7. customsubjected to phase separation
  8. washthe toluene layer was washed with 50 ml of hot water
  9. customsubjected to solvent removal

Sources & evidence

ORD record
ord-2a5436161bb9463b938f144aeabb85a9
Source dataset
uspto-grants-2003_06
Patent number
US06576765B2

Reaction notes

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