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

HRID 915541Notes

Reaction equation

HRID 915541 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>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

7

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 1

HCID 312751,4-DioxaneSolvent

Procedure

DEAD (0.43 ml) was added to a solution of triphenylphosphine (0.72 g), 3-chloro4-fluorophenol (0.403 g) and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (0.5 g) in THP at room temperature (RT). The resulting mixture was stirred overnight, HCl in dioxan (2 ml of 4M) was added and the mixture stirred at RT overnight. The mrixture 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 mrixture 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-db49792aa1da473f9c66f97f3d5c248a
Source dataset
uspto-grants-2007_09
Patent number
US07265227B2

Reaction notes

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