Dichloromethane → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy)-6-piperidinylcarbonyl-1-phenyl-8-azabicyclo[3.2.1]octane

HRID 2088191Notes

Reaction equation

HRID 2088191 reaction equation
FC(F)(F)C(O)=O.[CH2:8]([N:15]1[C@@H:20]2[C@H:21]([C:23]([OH:25])=O)[CH2:22][C@@:16]1([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C@H:17]([O:26][CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=1)[CH2:18][CH2:19]2)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.ClCCl.[NH:51]1[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]1.C(N(CC)CC)C.Cl.CN(C)CCCN=C=NCC>>[CH2:8]([N:15]1[C@@H:20]2[C@H:21]([C:23]([N:51]3[CH2:56][CH2:55][CH2:54][CH2:53][CH2:52]3)=[O:25])[CH2:22][C@@:16]1([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C@H:17]([O:26][CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:36])([F:35])[F:37])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=1)[CH2:18][CH2:19]2)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 8082PiperidineHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86586685(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxylic acid trifluoroacetate

Product 1

HCID 86586736(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy)-6-piperidinylcarbonyl-1-phenyl-8-azabicyclo[3.2.1]octaneYield 88%

Procedure

A 0.07M solution of (1R*,2R*,5S*,6R*)-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxylic acid trifluoroacetate (Example 53) in dichloromethane (2.5 ml, 0.18 mmol) was added to a mixture of piperidine (0.25 ml, 2.5 mmol), triethylamine (0.1 ml, 0.7 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (66 mg, 0.34 mmol), and 4-N,N-dimethylaminopyridine (12 mg, 0.1 mmol). The mixture was stirred at room temperature overnight and purified by chromatography on silica gel (iso-hexane:ethyl acetate) to give the title compound (100 mg, 88%).

Workup

  1. custompurified by chromatography on silica gel (iso-hexane:ethyl acetate)

Sources & evidence

ORD record
ord-ffdd2ece42734f6c9084062bf8711629
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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