Hydrochloric Acid → 4-(2-Chloro-4-fluorophenoxy)piperidine

HRID 968772Notes

Reaction equation

HRID 968772 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:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=1[OH:40].C(OC([N:48]1[CH2:53][CH2:52][CH:51](O)[CH2:50][CH2:49]1)=O)(C)(C)C.Cl>C1COCC1>[Cl:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=1[O:40][CH:51]1[CH2:52][CH2:53][NH:48][CH2:49][CH2:50]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 748142-Chloro-4-fluorophenolHCID 643502Tert-butyl 4-hydroxypiperidine-1-carboxylateHCID 5462977Diethyl azodicarboxylate

Product 1

HCID 223974264-(2-Chloro-4-fluorophenoxy)piperidineYield 85.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

DEAD (0.90 ml) was added to a solution of triphenylphosphine (1.44 g), 2-chloro-4-fluorophenol (0.806 g) and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (1.0 g) in THF at RT. The reaction was stirred for 16 hrs, HCl (2 ml, 4M in dioxan) added and the mixture stirred at RT for 16 hrs. The mixture was then evaporated to dryness, triethylamine (5 ml) added, re-evaporated, dissolved in methanol (10 ml) and placed on to a SCX cartridge (Varian, 10 g), eluted first with methanol then with 10% NH3 in methanol. The basic fractions were combined and evaporated to give the sub-title compound as an oil (0.98 g)

Workup

  1. stirringthe mixture stirred at RT for 16 hrs
  2. customThe mixture was then evaporated to dryness, triethylamine (5 ml)
  3. additionadded
  4. customre-evaporated
  5. dissolutiondissolved in methanol (10 ml)
  6. washeluted first with methanol
  7. customevaporated

Sources & evidence

ORD record
ord-c912137ede5e48f99a0c6274530d5ea2
Source dataset
uspto-grants-2007_12
Patent number
US07304077B2

Reaction notes

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