1,3-Cyclohexadiene → 6-((4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid

HRID 2045798Notes

Reaction equation

HRID 2045798 reaction equation
[CH:1]1([N:4]([C@H:31]2[C:40]3[CH:39]=[C:38]([F:41])[CH:37]=[CH:36][C:35]=3[N:34]([C:42](=[O:54])[C:43]3[CH:48]=[CH:47][C:46]([O:49][C:50]([F:53])([F:52])[F:51])=[CH:45][CH:44]=3)[C@H:33]3[CH2:55][CH2:56][CH2:57][C@@H:32]23)[C:5](=[O:30])[CH2:6][CH2:7][C:8]([O:10][CH:11]2[O:16][CH:15]([C:17]([O:19]CC3C=CC=CC=3)=[O:18])[CH:14]([OH:27])[CH:13]([OH:28])[CH:12]2[OH:29])=[O:9])[CH2:3][CH2:2]1.C1CCC=CC=1>[Pd].C(O)(C)C.C1(OC)CCCC1>[CH:1]1([N:4]([C@H:31]2[C:40]3[CH:39]=[C:38]([F:41])[CH:37]=[CH:36][C:35]=3[N:34]([C:42](=[O:54])[C:43]3[CH:44]=[CH:45][C:46]([O:49][C:50]([F:51])([F:53])[F:52])=[CH:47][CH:48]=3)[C@H:33]3[CH2:55][CH2:56][CH2:57][C@@H:32]23)[C:5](=[O:30])[CH2:6][CH2:7][C:8]([O:10][CH:11]2[O:16][CH:15]([C:17]([OH:19])=[O:18])[CH:14]([OH:27])[CH:13]([OH:28])[CH:12]2[OH:29])=[O:9])[CH2:3][CH2:2]1

Participants

6

Reactant 2

HCID 116051,3-CyclohexadieneHCID 71140109benzyl 6-((4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate

Product 1

HCID 711365346-((4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acidYield 67.9%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 3776IsopropanolSolventHCID 138539Cyclopentyl methyl etherSolvent

Conditions

Temperature
60 °C

Procedure

Palladium on carbon (80 mg, 0.752 mmol) was added to a stirred mixture of benzyl 6-((4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylate (0.23 g, 0.29 mmol) and cyclohexadiene (1.5 mL, 0.293 mmol) in isopropanol (7.5 mL) and cyclopentylmethyl ether (7.50 mL) and the mixture was stirred at 60° C. for 1 h. The mixture was filtered through a Celite® pad and washed with ether/isopropanol (1/1). Solvent was removed to give crude product which was purified using reverse phase HPLC to give 6-((4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoyl)oxy)-3,4,5-trihydroxytetrahydro-2H-pyran-2-carboxylic acid 174 (140 mg), [M+H]+=710.1.

Workup

  1. filtrationThe mixture was filtered through a Celite® pad
  2. washwashed with ether/isopropanol (1/1)
  3. customSolvent was removed
  4. customto give crude product which
  5. customwas purified

Sources & evidence

ORD record
ord-056b159a3185440ea9197d6ef3d855bb
Source dataset
uspto-grants-2013_11
Patent number
US08592383B2

Reaction notes

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