Hydrochloric Acid → 4-(3-Chloro-4-fluorophenoxy)piperidine

HRID 1293541Notes

Reaction equation

HRID 1293541 reaction equation
CCOC(/N=N/C(OCC)=O)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:32][C:33]1[CH:34]=[C:35]([OH:40])[CH:36]=[CH:37][C:38]=1[F:39].C(OC([N:48]1[CH2:53][CH2:52][CH:51](O)[CH2:50][CH2:49]1)=O)(C)(C)C.Cl>C1COCC1.O1CCOCC1>[Cl:32][C:33]1[CH:34]=[C:35]([CH:36]=[CH:37][C:38]=1[F:39])[O:40][CH:51]1[CH2:52][CH2:53][NH:48][CH2:49][CH2:50]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 757903-Chloro-4-fluorophenolHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 223975074-(3-Chloro-4-fluorophenoxy)piperidineYield 105.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 312751,4-DioxaneSolvent

Procedure

DEAD (0.43 ml) was added to a solution of triphenylphosphine (0.72 g), 3-chloro-4-fluorophenol (0.403 g) and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.5 g) in THF at RT. The resulting mixture was stirred overnight, HCl in dioxan (2 ml of 4M) was added and the mixture stirred at RT overnight. The mixture was then evaporated to dryness and triethylamine (5 ml) was added. The mixture was evaporated and the residue was dissolved in methanol (10 ml), placed onto a SCX cartridge (Varian, 10 g, SCX cartridge available from International Sorbent Technology Isolute® Flash SCX-2) and eluted: first with methanol then with 10% NH3 in methanol. The basic fractions were combined and evaporated to give the product as an oil (0.6 g).

Workup

  1. stirringthe mixture stirred at RT overnight
  2. customThe mixture was then evaporated to dryness and triethylamine (5 ml)
  3. additionwas added
  4. customThe mixture was evaporated
  5. dissolutionthe residue was dissolved in methanol (10 ml)
  6. washeluted
  7. customevaporated

Sources & evidence

ORD record
ord-0cabf8cb743a483396b9cf817a014560
Source dataset
uspto-grants-2007_07
Patent number
US07238811B2

Reaction notes

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