Trifluoroacetic acid → tert-butyl (3SR,4RS,5RS)-4-[4-(2-benzyloxy-ethoxymethyl)-phenyl]-3-hydroxymethyl-5-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate

HRID 1005241Notes

Reaction equation

HRID 1005241 reaction equation
C(OCCI)C1C=CC=CC=1.[CH2:12]([O:19][CH2:20][CH2:21][O:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([CH:30]2[CH:35]([CH2:36][O:37]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH2:34][N:33]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:32][CH:31]2[O:64][CH2:65][C:66]2[CH:75]=[CH:74][C:73]3[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=3)[CH:67]=2)=[CH:26][CH:25]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.FC(F)(F)C(O)=O.FC(F)(F)C(OC(=O)C(F)(F)F)=O>C(Cl)Cl>[CH2:12]([O:19][CH2:20][CH2:21][O:22][CH2:23][C:24]1[CH:25]=[CH:26][C:27]([CH:30]2[CH:31]([O:64][CH2:65][C:66]3[CH:75]=[CH:74][C:73]4[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=4)[CH:67]=3)[CH2:32][N:33]([C:57]([O:59][C:60]([CH3:61])([CH3:62])[CH3:63])=[O:58])[CH2:34][CH:35]2[CH2:36][OH:37])=[CH:28][CH:29]=1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 9845Trifluoroacetic anhydrideHCID 103553141-Benzyloxy-2-iodoethaneHCID 86604536tert-butyl (3RS,4RS,5SR)-4-[4-(2-benzyloxy-ethoxymethyl)-phenyl]-3-(naphthalen-2-ylmethoxy)-5-trityloxymethyl-piperidine-1-carboxylate

Product 1

HCID 86604535tert-butyl (3SR,4RS,5RS)-4-[4-(2-benzyloxy-ethoxymethyl)-phenyl]-3-hydroxymethyl-5-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

In an analogous manner to that described in Example 22 (d), from tert-butyl (3RS,4RS,5SR)-1-benzyl-4-(4-bromo-phenyl)-5-hydroxymethyl-piperidin-3-ol [Example 68 (e)] by a palladium catalyzed carbonylation with carbon monoxide in methanol there was obtained methyl (3RS,4RS,5SR)-4-(1-benzyl-3-hydroxy-5-hydroxymethyl-piperidin-4-yl)-benzoate, hydrogenolysis of which in the presence of 5% palladium-charcoal at atmospheric pressure in methanol analogously to Example 2 (e) gave methyl 4-(3-hydroxy-5-hydroxymethyl-piperidin-4-yl)-benzoate. Subsequent introduction of the BOC group analogously to Example 1 (f) yielded tert-butyl (3RS,4RS,5SR)-3-hydroxy-5-hydroxymethyl-4-(4-methoxycarbonyl-phenyl)-piperidine-1-carboxylate, from which by reaction with triphenylchloromethane analogously to Example 68 (i) there was obtained tert-butyl (3RS,4RS,5SR)-3-hydroxy-4-(4-methoxycarbonyl-phenyl)-5-trityloxymethyl-piperidine-1-carboxylate. Subsequent alkylation by means of 2-bromomethyl-naphthalene analogously to Example 1 (g) yielded tert-butyl (3RS,4RS,5SR)-4-(4-methoxycarbonyl-phenyl)-3-(naphthalen-2-ylmethoxy)-5-trityloxymethyl-piperidine-1-carboxylate, reduction of which with lithium borohydride analogously to Example 22 (e) yielded tert-butyl (3RS,4RS,5SR)-4-(4-hydroxymethyl-phenyl)-3-(naphthalen-2-ylmethoxy)-5-trityloxymethyl-piperidine-1-carboxylate as a colourless foam; MS: 737 (M+NH4)+. Further alkylation with 2-(benzyloxy)-ethyl iodide [Helv.Chim. Acta Vol.71, (1988), 2039] analogously to Example 1 (g) gave tert-butyl (3RS,4RS,5SR)-4-[4-(2-benzyloxy-ethoxymethyl)-phenyl]-3-(naphthalen-2-ylmethoxy)-5-trityloxymethyl-piperidine-1-carboxylate, from which after cleavage of the trityl group by means of a mixture of trifluoroacetic acid and trifluoroacetic anhydride in methylene chloride analogously to Example 86 (u) there was obtained tert-butyl (3SR,4RS,5RS)-4-[4-(2-benzyloxy-ethoxymethyl)-phenyl]-3-hydroxymethyl-5-(naphthalen-2-ylmethoxy)-piperidine-1-carboxylate as a colourless oil; MS: 629 (M+NH4)+.

Sources & evidence

ORD record
ord-23bb0104bb794b17a0dd5e83a8525302
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

Loading…