(3RS,4RS)-4-(4-Fluorophenyl)-3-(3-hydroxy-naphthalen-2-ylmethoxy)-piperidine → tert-butyl (3RS,4RS)-4-(4-aminomethyl-phenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate

HRID 1004973

Reaction equation

HRID 1004973 reaction equation
FC1C=CC(C2CCNCC2OCC2C(O)=CC3C(=CC=CC=3)C=2)=CC=1.[C:27]([C:29]1[CH:34]=[CH:33][C:32]([CH:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:46])[CH3:45])=[O:42])[CH2:37][CH:36]2[O:48][CH2:49][C:50]2[CH:59]=[CH:58][C:57]3[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=3)[CH:51]=2)=[CH:31][CH:30]=1)#[N:28]>O1CCCC1>[NH2:28][CH2:27][C:29]1[CH:34]=[CH:33][C:32]([CH:35]2[CH2:40][CH2:39][N:38]([C:41]([O:43][C:44]([CH3:47])([CH3:45])[CH3:46])=[O:42])[CH2:37][CH:36]2[O:48][CH2:49][C:50]2[CH:59]=[CH:58][C:57]3[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=3)[CH:51]=2)=[CH:31][CH:30]=1

Participants

4

Reactant 2

HCID 22126512(3RS,4RS)-4-(4-Fluorophenyl)-3-(3-hydroxy-naphthalen-2-ylmethoxy)-piperidineHCID 86604393tert-butyl (3RS,4RS)-4-(4-cyano-phenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate

Product 1

HCID 53800110tert-butyl (3RS,4RS)-4-(4-aminomethyl-phenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylateYield 79%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 1 33 mg (0.301 mmol) of tert-butyl (3RS,4RS)-4-(4-cyano-phenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate in 0.5 ml of tetrahydrofuran was treated with 1.5 ml (1.5 mmol) of a 1M borane-tetrahydrofuran complex solution in tetrahydrofuran and the mixture was heated to reflux under argon for 6 hours. The reaction mixture was partitioned between methylene chloride and water, the organic phase was dried over magnesium sulphate and finally the solvent was removed under reduced pressure. The crude product (163 mg) was purified by chromatography on silica gel with a 14:1:0.1 mixture of methylene chloride, methanol and a 25% ammonia solution as the eluent. There were obtained 106 mg (79% of theory) of tert-butyl (3RS,4RS)-4-(4-aminomethyl-phenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate as a colourless resin; MS: 447 (M+H)+.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux under argon for 6 hours
  3. customThe reaction mixture was partitioned between methylene chloride and water
  4. dry with materialthe organic phase was dried over magnesium sulphate
  5. customfinally the solvent was removed under reduced pressure
  6. customThe crude product (163 mg) was purified by chromatography on silica gel with a 14:1:0.1 mixture of methylene chloride, methanol

Sources & evidence

ORD record
ord-e8bbac5480934f17b3a3f6e96aa5fa3b
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Linked notes

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