Chloroacetyl chloride → HCID 66665363, compound

HRID 2196347Notes

Reaction equation

HRID 2196347 reaction equation
Cl.[NH2:2][C@@:3]([C:9]1[CH:14]=[C:13](Br)[CH:12]=[CH:11][C:10]=1[F:16])([CH:6]([F:8])[F:7])[CH2:4][OH:5].C([O-])([O-])=O.[K+].[K+].Cl[CH2:24][C:25](Cl)=[O:26]>O>[F:7][CH:6]([F:8])[C@:3]1([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[F:16])[NH:2][C:25](=[O:26])[CH2:24][O:5][CH2:4]1

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 11430Potassium CarbonateHCID 68007105HCID 68007105, compound

Product 1

HCID 66665363HCID 66665363, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Conditions

Temperature
25 °C

Procedure

To a suspension of (R)-2-amino-2-(5-bromo-2-fluoro-phenyl)-3,3-difluoro-propan-1-ol HCl salt (0.5 g, 1.56 mmol) in IPAc (5 ml) was added under argon a solution of K2CO3 (0.862 g, 6.24 mmol) in 5 ml water below 25° C. After stirring for 30 min at 25° C. to provide a diphase clear solution, cooled down to −5° C., a solution of 2-chloroacetyl chloride (0.41 g, 3.59 mmol) in IPAc (2 mL) was added slowly with the temperature below 10° C. After stirring for 30 min at 20° C., the organic phase was collected and used for next step directly. THF (3 ml) was added to the above solution, the mixture was cooled to 0° C. The solution was added under argon KOtBu (0.35 g, 3.12 mmol) below 10° C. After stirring at 20° C. for 3 h, water was added to quench the reaction. The organic phase was washed by 1N HCl water solution (5 ml). The organic phase was collected and used for next step directly. The above solution was added water (5 ml) and Pd/C (10%, 50 mg), the mixture was stirred under H2 (1.5 bar) at 25° C. for 3 h. The catalyst was filtered out. The filtration was washed by 15% NaCl water solution. The solvent was removed under vacuum to provide the title compound as yellowish solid. ESIMS: 246 [(M+H)+]. 1H NMR (400 MHz, DMSO-d6): δ 9.08 (s, 1H), 7.57 (m, 1H), 7.48 (m, 1H), 7.30 (m, 1H), 7.81 (m, 1H), 7.30 (m, 2H), 6.55 (t, 1H), 4.1 (m, 4H).

Workup

  1. customto provide a diphase clear solution
  2. temperaturecooled down to −5° C.
  3. stirringAfter stirring for 30 min at 20° C.
  4. customthe organic phase was collected
  5. additionTHF (3 ml) was added to the above solution
  6. temperaturethe mixture was cooled to 0° C
  7. additionThe solution was added under argon KOtBu (0.35 g, 3.12 mmol) below 10° C
  8. stirringAfter stirring at 20° C. for 3 h
  9. customto quench
  10. customthe reaction
  11. washThe organic phase was washed by 1N HCl water solution (5 ml)
  12. customThe organic phase was collected
  13. additionThe above solution was added water (5 ml) and Pd/C (10%, 50 mg)
  14. stirringthe mixture was stirred under H2 (1.5 bar) at 25° C. for 3 h
  15. filtrationThe catalyst was filtered out
  16. filtrationThe filtration
  17. washwas washed by 15% NaCl water solution
  18. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-5ee3cfca0e55416c80c6b406b6c8eb11
Source dataset
uspto-grants-2012_12
Patent number
US08338413B1

Reaction notes

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