Water → HCID 16755736, compound

HRID 1174829Notes

Reaction equation

HRID 1174829 reaction equation
[NH2:1][C@@H:2]([CH:5]([C:10]([F:13])([F:12])[F:11])[C:6]([F:9])([F:8])[F:7])[CH2:3][OH:4].CN1CCOCC1.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([S:28](Cl)(=[O:30])=[O:29])=[CH:24][CH:23]=1.O>C(OC(C)C)(=O)C>[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([S:28]([NH:1][C@H:2]([CH2:3][OH:4])[CH:5]([C:6]([F:7])([F:8])[F:9])[C:10]([F:11])([F:12])[F:13])(=[O:30])=[O:29])=[CH:24][CH:23]=1

Participants

6

Reactant 4

HCID 962WaterHCID 73984-Chlorobenzenesulfonyl chlorideHCID 79724-MethylmorpholineHCID 25022953HCID 25022953, compound

Product 1

HCID 16755736HCID 16755736, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 7915Isopropyl AcetateSolvent

Conditions

Temperature
22.5 °C

Procedure

To a suspension of (2S)-2-amino-4,4,4-tri-fluoro-3-(trifluoromethyl)butan-1-ol (5 g, 20.2 mmol) in isopropyl acetate (50 mL) was added 4-methyl morpholine (5 mL, 45.5 mmol). The mixture was stirred at 20 to 25° C. for 5 to 10 minutes and then 4-chlorobenzenesulfonyl chloride (4.5 g, 21.3 mmol) was added. The reaction mixture was stirred at 20 to 25° C. for 6 to 18 hours. Water (25 mL) was added to the reaction mixture and the solid dissolved. The two layers were separated, the organic layer was washed with 10% NaHCO3 (25 mL) and 10% NaCl (25 mL), and heptane (50 mL) was added to the isopropyl acetate layer (about 50 mL). The mixture was reduced in volume by about half by distillation at atmospheric conditions. While the solution remained at 80 to 90° C., heptane (50 mL) was added over 5 to 10 minutes. A solid began to form during heptane addition. After addition, the mixture was cooled to 20 to 25° C., the solution was stirred for 1 to 2 hours, and then further cooled to 5 to 10° C. for 1 hours. The solid was collected by filtration, washed with heptane (15 mL), and oven-dried to give 6.44 g (83%) of an off-white solid. 98% area HPLC purity.

Workup

  1. stirringThe reaction mixture was stirred at 20 to 25° C. for 6 to 18 hours
  2. dissolutionthe solid dissolved
  3. customThe two layers were separated
  4. washthe organic layer was washed with 10% NaHCO3 (25 mL) and 10% NaCl (25 mL), and heptane (50 mL)
  5. additionwas added to the isopropyl acetate layer (about 50 mL)
  6. distillationThe mixture was reduced in volume by about half by distillation at atmospheric conditions
  7. customremained at 80 to 90° C.
  8. additionheptane (50 mL) was added over 5 to 10 minutes
  9. customto form during heptane addition
  10. additionAfter addition
  11. temperaturethe mixture was cooled to 20 to 25° C.
  12. stirringthe solution was stirred for 1 to 2 hours
  13. temperaturefurther cooled to 5 to 10° C. for 1 hours
  14. filtrationThe solid was collected by filtration
  15. washwashed with heptane (15 mL)
  16. customoven-dried

Sources & evidence

ORD record
ord-0343def7866d44fe8ac22b88050922d3
Source dataset
uspto-grants-2010_11
Patent number
US07838550B2

Reaction notes

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