Benzyl Alcohol → HCID 71117581, compound

HRID 2045791Notes

Reaction equation

HRID 2045791 reaction equation
[C:1](Cl)(Cl)=[O:2].[F:5][C:6]1[CH:7]=[CH:8][C:9]2[C:10](=[O:19])[C@H:11]3[CH2:18][CH2:17][CH2:16][C@H:12]3[NH:13][C:14]=2[CH:15]=1.C(N(C(C)C)CC)(C)C.[CH2:29]([OH:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[H-].[Na+].Cl>C1COCC1>[F:5][C:6]1[CH:7]=[CH:8][C:9]2[C:10](=[O:19])[C@H:11]3[CH2:18][CH2:17][CH2:16][C@H:12]3[N:13]([C:1]([O:36][CH2:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[O:2])[C:14]=2[CH:15]=1

Participants

8

Reactant 6

HCID 244Benzyl AlcoholHCID 313Hydrochloric AcidHCID 6371PhosgeneHCID 24758Sodium hydrideHCID 81531DiisopropylethylamineHCID 71139024HCID 71139024, compound

Product 1

HCID 71117581HCID 71117581, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
23 °C

Procedure

Phosgene (20% in toluene, 1.0 g, 2.2 mmol, 1.5 equiv) was added to a solution of cis-6-fluoro-1,2,3,3a,4,9a-hexahydro-9H-cyclopenta[b]quinolin-9-one 6B (300 mg, 1.5 mmol, 1 equiv) and diisopropyl ethylamine (380 uL, 2.2 mmol, 1.5 equiv) in THF (14.6 mL). After stirring at 23° C. for two hours the solution was treated with benzyl alcohol (450 μL, 4.4 mmol, 3 equiv) and sodium hydride (60% in mineral oil, 230 mg, 5.9 mmol, 4 equiv). After stirring at 23° C. for 12 hours the reaction was neutralized to pH=7 with 1N HCl. The reaction mixture was then partitioned between ethyl acetate and water. The organic layer was washed with saturated aqueous sodium chloride solution, and the washed solution was dried over sodium sulfate. The dried solution was filtered, and the filtrate was concentrated. The filtrate was purified by flash-column chromatography (hexanes, grading to 50% ethyl acetate-hexanes) to afford 6C. [M+H]+: 340.2.

Workup

  1. stirringAfter stirring at 23° C. for 12 hours the reaction
  2. customThe reaction mixture was then partitioned between ethyl acetate and water
  3. washThe organic layer was washed with saturated aqueous sodium chloride solution
  4. dry with materialthe washed solution was dried over sodium sulfate
  5. filtrationThe dried solution was filtered
  6. concentrationthe filtrate was concentrated
  7. customThe filtrate was purified by flash-column chromatography (hexanes, grading to 50% ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-50c60f7bf2304a05a4db3db9faa009e6
Source dataset
uspto-grants-2013_11
Patent number
US08592383B2

Reaction notes

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