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

HRID 1004987Notes

Reaction equation

HRID 1004987 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][O:12][CH:13]1[CH:18]([C:19]2[CH:24]=[CH:23][C:22]([CH2:25][O:26]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:21][CH:20]=2)[CH2:17][CH2:16][N:15]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH2:14]1.Cl.C(=O)([O-])[O-].[Na+].[Na+]>C(Cl)Cl.CO>[OH:26][CH2:25][C:22]1[CH:23]=[CH:24][C:19]([CH:18]2[CH2:17][CH2:16][N:15]([C:46]([O:48][C:49]([CH3:52])([CH3:50])[CH3:51])=[O:47])[CH2:14][CH:13]2[O:12][CH2:11][C:2]2[CH:3]=[CH:4][C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[CH:1]=2)=[CH:20][CH:21]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 10340Sodium CarbonateHCID 54015520tert-butyl (3RS,4RS)-3-naphthalen-2-ylmethoxy-4-(4-trityloxymethyl-phenyl)-piperidine-1-carboxylate

Product 1

HCID 53699338tert-butyl (3RS,4RS)-4-(4-hydroxymethyl-phenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylateYield 87.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1.07 g (1.48 mmol) of tert-butyl (3RS,4RS)-3-naphthalen-2-ylmethoxy-4-(4-trityloxymethyl-phenyl)-piperidine-1-carboxylate in 15 ml of methylene chloride was treated at room temperature with 2 ml of 2N hydrogen chloride in methanol and the mixture was stirred at room temperature for 15 minutes. Subsequently, the solution was poured into 30 ml of saturated sodium carbonate solution and this was extracted twice with 50 ml of ethyl acetate each time. The combined organic phases were dried over sodium sulphate and evaporated under reduced pressure. For purification, the crude product was chromatographed on silica gel using a 99:1 mixture of methylene chloride and methanol as the eluent. There were obtained 580 mg (82% of theory) of tert-butyl (3RS,4RS)-4-(4-hydroxymethyl-phenyl)-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate as a colourless oil; MS: 447 (M)+.

Workup

  1. extractionthis was extracted twice with 50 ml of ethyl acetate each time
  2. dry with materialThe combined organic phases were dried over sodium sulphate
  3. customevaporated under reduced pressure
  4. customFor purification
  5. customthe crude product was chromatographed on silica gel using
  6. additiona 99:1 mixture of methylene chloride and methanol as the eluent

Sources & evidence

ORD record
ord-1391144d6ab9472aad627940a5690ec2
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

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