Trifluoroacetic acid → (1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxylic acid 2-acetylhydrazide

HRID 2088173Notes

Reaction equation

HRID 2088173 reaction equation
[F:1][C:2]([F:40])([F:39])[C:3]1[CH:4]=[C:5]([CH2:13][O:14][CH:15]2[CH2:21][CH2:20][CH:19]3[N:22]([CH2:23][CH:24]=[CH2:25])[C:16]2([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH2:17][CH:18]3[C:26]([O:28]C(C)(C)C)=O)[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.F[C:42](F)(F)[C:43](O)=O.[C:48]([NH:51][NH2:52])(=[O:50])[CH3:49].[CH2:53](N(CC)CC)[CH3:54].Cl.CN(C)CCCN=C=NCC>ClCCl>[C:48]([NH:51][NH:52][C:26]([C@@H:18]1[CH2:17][C@:16]2([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[N:22]([CH2:23][C:24]3[CH:25]=[CH:43][CH:42]=[CH:54][CH:53]=3)[C@H:19]1[CH2:20][CH2:21][C@H:15]2[O:14][CH2:13][C:5]1[CH:4]=[C:3]([C:2]([F:1])([F:40])[F:39])[CH:8]=[C:7]([C:9]([F:11])([F:12])[F:10])[CH:6]=1)=[O:28])(=[O:50])[CH3:49]

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 14039AcetohydrazideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 865867082-{[3,5-Bis(trifluoromethyl)phenyl]methoxy}-6-(tert-butoxycarbonyl)-1-phenyl-8-(prop-2-enyl)-8-azabicyclo[3.2.1]octane

Product 1

HCID 86586709(1R*,2R*,5S*,6R*)-8-Benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octan-6-carboxylic acid 2-acetylhydrazideYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (1R*,2R*,5S*,6RS*)-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-6-(tert-butoxycarbonyl)-1-phenyl-8-(prop-2-enyl)-8-azabicyclo[3.2.1]octane (Example 81), trifluoroacetic acid (4 ml) and dichloromethane (6 ml) was stirred at room temperature overnight and concentrated in vacuo. The residue was treated with acetic hydrazide (164 mg, 2.21 mmol), triethylamine (0.5 ml, 3.6 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (350 mg, 1.8 mmol), and 4-N,N-dimethylaminopyridine (47 mg, 0.38 mmol). The mixture was stirred for 5 hours, quenched with saturated aqueous NaHCO3 and extracted into dichloromethane. The combined organic extracts were dried (Na2SO4) and concentrated. The residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate) to give the title compound (180 mg, 50%).

Workup

  1. concentrationconcentrated in vacuo
  2. stirringThe mixture was stirred for 5 hours
  3. customquenched with saturated aqueous NaHCO3
  4. extractionextracted into dichloromethane
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography on silica gel (iso-hexane:ethyl acetate)

Sources & evidence

ORD record
ord-96b795a52b8b4dbc8e8e3cbd6f6eb5cd
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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