2-Bromomethylnaphthalene → HCID 86604533, compound

HRID 1005240Notes

Reaction equation

BrCC1C=CC2C(=CC=CC=2)C=1.C[O:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[CH:28]([CH2:29][O:30][C:31]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:27][N:26]([C:50]([O:52][C:53]([CH3:56])([CH3:55])[CH3:54])=[O:51])[CH2:25][CH:24]2[O:57][CH2:58][C:59]2[CH:68]=[CH:67][C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[CH:60]=2)=[CH:19][CH:18]=1)=O.[BH4-].[Li+]>>[OH:14][CH2:15][C:17]1[CH:22]=[CH:21][C:20]([CH:23]2[CH:28]([CH2:29][O:30][C:31]([C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[C:44]3[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=3)[CH2:27][N:26]([C:50]([O:52][C:53]([CH3:56])([CH3:54])[CH3:55])=[O:51])[CH2:25][CH:24]2[O:57][CH2:58][C:59]2[CH:68]=[CH:67][C:66]3[C:61](=[CH:62][CH:63]=[CH:64][CH:65]=3)[CH:60]=2)=[CH:19][CH:18]=1

Participants

Reactant 3

HCID 703202-Bromomethylnaphthalene

HCID 4148881Lithium borohydride

HCID 86604534HCID 86604534, compound

Product 1

HCID 86604533HCID 86604533, compound

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-a3c03d225b8044278b318a694dc4063a
Source dataset: uspto-grants-2000_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06051712

Reaction notes

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