HCID 86604456, compound → HCID 86604455, compound

HRID 1005131Notes

Reaction equation

HRID 1005131 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:14][CH:13]3[N:15]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:10]([CH2:11][CH2:12]3)[CH:9]2[OH:23])=[CH:4][CH:3]=1.[C]=O>CO.[Pd]>[OH:23][CH:9]1[CH:8]([C:5]2[CH:6]=[CH:7][C:2]([C:16]([O:18][CH3:19])=[O:17])=[CH:3][CH:4]=2)[CH2:14][CH:13]2[N:15]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:10]1[CH2:11][CH2:12]2

Participants

5

Reactant 2

HCID 86604456HCID 86604456, compoundHCID 178418416HCID 178418416, compound

Product 1

HCID 86604455HCID 86604455, compound

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

(eee) In an analogous manner to that described in Example 12 (c)-(d), cleavage of the N-methyl group from (1RS,2RS,3RS,5SR)-3-(4-bromo-phenyl)-8-methyl-8-aza-bicyclo[3.2.1]octan-2-ol, obtained analogously to the 4-chlorophenyl derivative [J.Org.Chem. 35, 802 (1970)], was effected by firstly synthesizing (1RS,2RS,3RS,5SR)-3-(4-bromo-phenyl)-2-(2,2,2-trichloro-ethoxycarbonyloxy)-8-aza-bicyclo[3.2.1]octane-8-carboxylate by reaction with 2,2,2-trichloroethyl chloroformate and subsequently reacting with zinc in glacial acetic acid to give (1RS,2RS,3RS,5SR)-3-(4-bromo-phenyl)-8-aza-bicyclo[3.2.1]octan-2-ol. Subsequent introduction of the BOC group analogously to Example 1 (f) gave tert-butyl (1RS,2RS,3RS,5SR)-3-(4-bromo-phenyl)-2-hydroxy-8-aza-bicyclo[3.2.1]octane-8-carboxylate, palladium-catalyzed carbonylation of which with carbon monoxide in methanol analogously to Example 22 (d) yielded tert-butyl (1RS,2RS,3RS,5SR)-2-hydroxy-3-(4-methoxycarbonyl-phenyl)-8-aza-bicyclo[3.2.1]octane-8-carboxylate. Subsequent reduction with lithium borohydride analogously to Example 22 (e) gave tert-butyl (1RS,2RS,3RS,5SR)-2-hydroxymethyl-phenyl)-8-aza-bicyclo[3.2.1]octane-8-carboxylate, reaction of which with trityl chloride analogously to Example 22 (h) gave tert-butyl (1RS,2RS,3RS,5SR)-2-hydroxy-3-(4-trityloxymethyl)-phenyl)-8-aza-bicyclo[3.2.1]octane-8-carboxylate. Further reaction with 2-bromomethyl-naphthalene analogously to Example 1 (9) gave tert-butyl (1RS,2RS,3RS,5SR)-2-(naphthalen-2-ylmethoxy)-3-(4-trityloxymethyl-phenyl)-8-aza-bicyclo[3.2.1]octane-8-carboxylate. In an analogous manner to that described in Example 86 (u) (b), by cleavage of the trityl group with a mixture of trifluoroacetic acid and trifluoroacetic anhydride there was obtained tert-butyl (1RS,2RS,3RS,5SR)-3-(4-hydroxymethyl-phenyl)-2-(naphthalen-2-ylmethoxy)-8-aza-bicyclo[3.2.1]octane-8-carboxylate, alkylation of which with benzyl 3-bromopropyl ether analogously to Example 44 (e) gave tert-butyl (1RS,2RS,3RS,5SR)-3-[4-(2-benzyloxy-propoxy-methyl)-phenyl]-2-(naphthalen-2-ylmethoxy)-8-aza-bicyclo-[3.2.1]octane-8-carboxylate as a colourless oil.

Sources & evidence

ORD record
ord-e1cca7d9e4934c92b99f3c6803796922
Source dataset
uspto-grants-2000_04
Patent number
US06051712

Reaction notes

Loading…