Hydrochloric Acid → tert-butyl (3RS,4RS)-3-(1,4-dimethoxy-naphthalen-2-ylmethoxy)-4-(4-hydroxy-phenyl)-piperidine-1-carboxylate

HRID 1005248Notes

Reaction equation

HRID 1005248 reaction equation
C([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]2[O:24][CH2:25][C:26]2[CH:35]=[C:34]([O:36][CH3:37])[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]=2[O:38][CH3:39])=[CH:7][CH:6]=1)C=C.N12CCN(CC1)CC2.Cl>C(O)C.CC(O)=O.CC(O)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[CH3:39][O:38][C:27]1[C:28]2[C:33](=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:34]([O:36][CH3:37])=[CH:35][C:26]=1[CH2:25][O:24][CH:12]1[CH:11]([C:8]2[CH:7]=[CH:6][C:5]([OH:4])=[CH:10][CH:9]=2)[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 9237DabcoHCID 53648544tert-butyl (3RS,4RS)-4-(4-allyloxy-phenyl)-3-(1,4-dimethoxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylate

Product 1

HCID 54373685tert-butyl (3RS,4RS)-3-(1,4-dimethoxy-naphthalen-2-ylmethoxy)-4-(4-hydroxy-phenyl)-piperidine-1-carboxylateYield 91%

Reagents, catalysts & solvents 2

HCID 10865532Bis(triphenylphosphine)palladium(II) diacetateCatalystHCID 702EthanolSolvent

Conditions

Temperature
2.5 °C

Procedure

A solution of 315 mg (0.59 mmol) of tert-butyl (3RS,4RS)-4-(4-allyloxy-phenyl)-3-(1,4-dimethoxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylate, 44 mg (0.059 mmol) of bis-(triphenylphosphine)-palladium(II) diacetate and 132 mg (1.18 mmol) of 1,4-diazabicyclo [2.2.2]octane in 10 ml of 95% ethanol was heated to reflux under argon for 2 hours. Subsequently, the reaction mixture was cooled to 0-5° C. and treated with 0.6 ml of 1N hydrochloric acid. Thereafter, the solvent was distilled off under reduced pressure and the residue was partitioned between ethyl acetate and water. After extraction and drying of the organic phase over sodium sulphate it was evaporated under reduced pressure. The residue was purified on silica gel using a 9:1 mixture of methylene chloride and ether as the eluent. There were obtained 265 mg (91% of theory) of tert-butyl (3RS,4RS)-3-(1,4-dimethoxy-naphthalen-2-ylmethoxy)-4-(4-hydroxy-phenyl)-piperidine-1-carboxylate as a yellowish foam; MS: 494 (M+H)+.

Workup

  1. temperatureto reflux under argon for 2 hours
  2. distillationThereafter, the solvent was distilled off under reduced pressure
  3. customthe residue was partitioned between ethyl acetate and water
  4. extractionAfter extraction
  5. dry with materialdrying of the organic phase over sodium sulphate it
  6. customwas evaporated under reduced pressure
  7. customThe residue was purified on silica gel using
  8. additiona 9:1 mixture of methylene chloride and ether as the eluent

Sources & evidence

ORD record
ord-2149c1d500ed40cf9a2695ccd96043d8
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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