Ammonia → 2,2-difluoro-2-pyridin-2-yl-ethylamine benzenesulphonate, (1:1 salt)

HRID 45574

Reaction equation

HRID 45574 reaction equation
C[C:2]1[CH:7]=[CH:6][C:5]([S:8]([O:11][CH2:12][C:13]([F:21])([F:20])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[Na+].[I-].[NH3:24].C1(S(O)(=O)=O)C=CC=CC=1>C(OC(C)C)(=O)C.CS(C)=O>[C:5]1([S:8]([OH:11])(=[O:10])=[O:9])[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1.[F:20][C:13]([F:21])([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=1)[CH2:12][NH2:24]

Participants

7

Reactant 4

HCID 222Ammonia2×HCID 5238Sodium IodideHCID 7371Benzenesulfonic AcidHCID 582496422,2-Difluoro-2-pyridin-2-ylethyl 4-methylbenzenesulfonate

Product 1

HCID 783578632,2-difluoro-2-pyridin-2-yl-ethylamine benzenesulphonate, (1:1 salt)Yield 49.5%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 7915Isopropyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

10 g of 2,2-Difluoro-2-pyridin-2-ylethyl 4-methylbenzenesulfonate (J) obtained in step 3, 5 g of NaI, 20 mL of DMSO and 90 mL of aqueous ammonia were taken in a 500 mL autoclave vessel. The reaction mixture was heated to 80° C. and a pressure of 15 to 17 kg of ammonia maintained for 30-40 hours. The volume of the reaction mass was reduced by vacuum distillation. The RM was washed with 60 mL of IPE. The pH of the RM was adjusted to 10-14 by adding a 50% NaOH solution and extracted three times with 60 mL of MDC. The combined MDC layers were washed with brine, dried over sodium sulphate and distilled under vacuum (crude weight=8 g). The crude mass obtained was dissolved with 10 mL of MDC, and to this 4.5 g benzene sulphonic acid (BSA) dissolved in 30 mL isopropyl acetate (IPAc) was added dropwise over a period of 30 minutes with stirring at RT. The RM was stirred for 30 minutes at RT. The solid obtained was filtered and washed with IPAc and dried under vacuum, resulting in 5 g of the titled compound (Yield=49.5%).

Workup

  1. distillationThe volume of the reaction mass was reduced by vacuum distillation
  2. washThe RM was washed with 60 mL of IPE
  3. additionby adding a 50% NaOH solution
  4. extractionextracted three times with 60 mL of MDC
  5. washThe combined MDC layers were washed with brine
  6. dry with materialdried over sodium sulphate
  7. distillationdistilled under vacuum (crude weight=8 g)
  8. customThe crude mass obtained
  9. dissolutionwas dissolved with 10 mL of MDC
  10. additionwas added dropwise over a period of 30 minutes
  11. stirringThe RM was stirred for 30 minutes at RT
  12. customThe solid obtained
  13. filtrationwas filtered
  14. washwashed with IPAc
  15. customdried under vacuum

Sources & evidence

ORD record
ord-ac1aafe395f44b6fa336ed0ef1904144
Source dataset
uspto-grants-2013_09
Patent number
US08541580B2

Linked notes

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