p-Toluenesulfonic acid → 2,2,2-trichloro-ethyl (3RS,4RS)-4-[3-(2-hydroxy-ethoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate

HRID 1858680Notes

Reaction equation

HRID 1858680 reaction equation
[NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([OH:7])[CH2:2]1.Br[CH2:9][C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH:11]=1.N1CCCCC1.Cl[C:27]([O:29][CH2:30][C:31]([Cl:34])([Cl:33])[Cl:32])=[O:28].[C:35](=[O:38])([O-])[O-].[K+].[K+].N1([C:47]([O-])=[O:48])CCCCC1.[C:50]1(C)[CH:55]=[CH:54][C:53](S(O)(=O)=O)=[CH:52][CH:51]=1>C(OCC)(=O)C.C(Cl)Cl>[OH:48][CH2:47][CH2:35][O:38][C:50]1[CH:55]=[C:54]([CH:4]2[CH2:5][CH2:6][N:1]([C:27]([O:29][CH2:30][C:31]([Cl:34])([Cl:33])[Cl:32])=[O:28])[CH2:2][CH:3]2[O:7][CH2:9][C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[CH:11]=2)[CH:53]=[CH:52][CH:51]=1

Participants

10

Reactant 7

HCID 6101p-Toluenesulfonic acidHCID 8082PiperidineHCID 11430Potassium CarbonateHCID 232933-HydroxypiperidineHCID 703202-BromomethylnaphthaleneHCID 870632,2,2-Trichloroethyl chloroformateHCID 21874245Piperidine carboxylate

Product 1

HCID 539217082,2,2-trichloro-ethyl (3RS,4RS)-4-[3-(2-hydroxy-ethoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

From 1-benzyl-4-(3-methoxy-phenyl)-piperidin-3-ol by cleavage of the methyl ether (RS)- and (SR)-methoxy-phenyl-acetate boron tribromide in methylene chloride there was obtained (3RS,4RS)-1-benzyl-4-(3-hydroxy-phenyl)-piperidin-3-ol as a pale yellow solid; MS: 283 (M)+. Alkylation with rac.-2-(2-iodo-ethoxy)-tetrahydro-pyran in the presence of potassium carbonate gave a mixture of (3RS,4RS)-1-benzyl-4-[3-[2-[(RS)- and -[(SR)-tetrahydro-pyran-2-yloxy]-ethoxy]-phenyl]-piperidin-3-ol as a colourless oil; MS: 410 (M-H)+. By subsequent alkylation with 2-bromomethylnaphthalene in an analogous manner to that described in Example 22(i) there was obtained a mixture of (3RS,4RS)-1-benzyl-3-(naphthalen-2-ylmethoxy)-4-[3-[2-[(RS)- and -[(SR)-tetrahydro-pyran-2-yloxy]-ethoxy]-phenyl]-piperidine as a colourless oil; MS: 552 (M)+. Then, by cleavage of the benzyl group using 2,2,2-trichloroethyl chloroformate and potassium carbonate in an analogous manner to that described in Example 25(a) there was obtained a mixture of 2,2,2-trichloroethyl (3RS,4RS)-3-(naphthalen-2-ylmethoxy)-4-[3-[2-[(RS)- and -[(SR)-tetrahydro-pyran-2-yloxy]-ethoxy]-phenyl]-piperidine-1-carboxylate; Rf : 0.60 (SiO2, methylene chloride:ethyl acetate=2:1). By subsequent cleavage of the THP group using p-toluenesulphonic acid there was obtained 2,2,2-trichloro-ethyl (3RS,4RS)-4-[3-(2-hydroxy-ethoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate. Finally, by reaction with pyridine-2-carbonyl azide in an analogous manner to that described in Example 24(m) there was obtained 2,2,2-trichloro-ethyl (3RS,4RS)-3-(naphthalen-2-ylmethoxy)-4-[3-(2-pyridin-2-ylcarbamoyloxy-ethoxy]-phenyl]-piperidine-1-carboxylate; Rf : 0.45 (SiO2, methylene chloride:ethyl acetate=9:1).

Workup

  1. customwas obtained
  2. customwas obtained

Sources & evidence

ORD record
ord-9596e2d8b46e4023bbb89ef465c75bb7
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

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