Hydrochloric Acid → 1-N-Phenoxycarbonyl-4-(2-amino-4-fluorophenoxy)-4-ethynylpiperidine

HRID 1193554Notes

Reaction equation

HRID 1193554 reaction equation
CO.[O:3]([C:10]([N:12]1[CH2:17][CH2:16][C:15]([C:29]#[CH:30])([O:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[N+:26]([O-])=O)[CH2:14][CH2:13]1)=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl>O.[Fe]>[O:3]([C:10]([N:12]1[CH2:17][CH2:16][C:15]([O:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[NH2:26])([C:29]#[CH:30])[CH2:14][CH2:13]1)=[O:11])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 887MethanolHCID 142814891-N-Phenoxycarbonyl-4-ethynyl-4-(4-fluoro-2-nitrophenoxy)piperidine

Product 1

HCID 142814961-N-Phenoxycarbonyl-4-(2-amino-4-fluorophenoxy)-4-ethynylpiperidineYield 33%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Procedure

To a stirred suspension of 735 ml of methanol and 51.7 g of 1-N-phenoxycarbonyl-4-ethynyl-4-(4-fluoro-2-nitrophenoxy)piperidine was added a solution of 51 ml of concentrated hydrochloric acid in 206 ml of water. To the stirred mixture was added, in aliquots, 80.2 g of iron (reduced, electrolytic). The mixture was stirred 2 hr, heated to 45° for 1 hr and allowed to cool to room temperature. The mixture was poured into ice/water, extracted twice with dichloromethane, washed with saturated sodium chloride solution and dried over anhydrous potassium carbonate. The mixture was filtered and the filtrate was evaporated. The residue was purified by chromatography on a Waters Prep 500 High Pressure Liquid Chromatograph (1×500 cc silica gel: eluent: 0.5 methanol/dichloromethane). Concentration of the appropriate fractions provided an oil, which crystallized on standing to provide 15.7 g (33%) of product. Recrystallization from cyclohexane/ethyl acetate provided the analytical sample, mp 125°-127°.

Workup

  1. temperatureheated to 45° for 1 hr
  2. extractionextracted twice with dichloromethane
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried over anhydrous potassium carbonate
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated
  7. customThe residue was purified by chromatography on a Waters Prep 500 High Pressure Liquid Chromatograph (1×500 cc silica gel: eluent: 0.5 methanol/dichloromethane)
  8. customConcentration of the appropriate fractions provided an oil, which
  9. customcrystallized

Sources & evidence

ORD record
ord-40bb8c9e48a14b0d8745077f59e94563
Source dataset
uspto-grants-1989_03
Patent number
US04810792

Reaction notes

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