Carbonochloridate → 2,2,2-trichloroethyl (3RS,4RS)-4-[3-(3-hydroxy-propoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate

HRID 1858684Notes

Reaction equation

HRID 1858684 reaction equation
C(N1CCC(C2C=CC=C(OCCCOC3CCCCO3)C=2)C(OCC2C=CC3C(=CC=CC=3)C=2)C1)C1C=CC=CC=1.ClC([O-])=O.[CH:47]1[C:56]2[C:51](=[CH:52][CH:53]=[CH:54][CH:55]=2)[CH:50]=[CH:49][C:48]=1[CH2:57][O:58][CH:59]1[CH:64]([C:65]2[CH:70]=[CH:69][CH:68]=[C:67]([O:71][CH2:72][CH2:73][CH2:74][O:75]C3CCCCO3)[CH:66]=2)[CH2:63][CH2:62][N:61]([C:82]([O:84][CH2:85][C:86]([Cl:89])([Cl:88])[Cl:87])=[O:83])[CH2:60]1>>[OH:75][CH2:74][CH2:73][CH2:72][O:71][C:67]1[CH:66]=[C:65]([CH:64]2[CH2:63][CH2:62][N:61]([C:82]([O:84][CH2:85][C:86]([Cl:87])([Cl:88])[Cl:89])=[O:83])[CH2:60][CH:59]2[O:58][CH2:57][C:48]2[CH:49]=[CH:50][C:51]3[C:56](=[CH:55][CH:54]=[CH:53][CH:52]=3)[CH:47]=2)[CH:70]=[CH:69][CH:68]=1

Participants

4

Reactant 3

HCID 21226386CarbonochloridateHCID 221269471-Benzyl-3-(naphthalen-2-ylmethoxy)-4-{3-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-phenyl}-piperidineHCID 221273692,2,2-Trichloroethyl 3-(naphthalen-2-ylmethoxy)-4-{3-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-phenyl}-piperidine-1-carboxylate

Product 1

HCID 542319762,2,2-trichloroethyl (3RS,4RS)-4-[3-(3-hydroxy-propoxy)-phenyl]-3-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate

Procedure

In an analogous manner to that described in Example 14, by alkylating (3RS,4RS)-1-benzyl-4-(3-hydroxy-phenyl)-piperidin-3-ol with rac.-2-(3-bromo-propoxy)-tetrahydro-pyran in the presence of potassium carbonate there was obtained a mixture of the diastereomeric racemates of (3RS,4RS)-1-benzyl-4-{3-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-phenyl}-piperidin-3-ol as a colourless oil; Rf : 0.38 (hexane:acetone=1:1). Subsequent alkylation with 2-bromomethylnaphthalene analogously to Example 12(b) gave a mixture of the diastereomeric racemates of 1-benzyl-3-(naphthalen-2-ylmethoxy)-4-{3-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-phenyl}-piperidine as a colourless oil; MS: 566 (M+H)+. Subsequent reaction with 2,2,2-trichloroethyl (sic) chloroformate analogously to Example 12(c) yielded a mixture of the diastereomeric racemates of 2,2,2-trichloroethyl 3-(naphthalen-2-ylmethoxy)-4-{3-[3-(tetrahydro-pyran-2-yloxy)-propoxy]-phenyl}-piperidine-1-carboxylate which, without further purification and characterization, was reacted with p-toluenesulphonic acid analogously to Example 53(c) to give 2,2,2-trichloroethyl (3RS,4RS)-4-[3-(3-hydroxy-propoxy)-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-trichloroethyl (3RS,4RS)-3-(naphthalen-2-ylmethoxy)-4-{3-[3-(pyridin-2-ylcarbamoyloxy)-propoxy]-phenyl}-piperidine-1-carboxylate as a colourless oil; Rf : 0.55 (methylene chloride:ethyl acetate=1:1).

Workup

  1. customyielded
  2. customwithout further purification and characterization
  3. customwas reacted with p-toluenesulphonic acid analogously to Example 53(c)

Sources & evidence

ORD record
ord-e067567a5f80436db97750a4e96345f5
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

Loading…