Hexafluoroacetone → HCID 117940104, compound

HRID 62286Notes

Reaction equation

HRID 62286 reaction equation
Cl[C:2]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:3]=1[CH2:4][CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][C:9]([O:20][CH3:21])=[C:10]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH:11]=2)[C:6]1=[O:22].[Li]CCCC.[F:36][C:37]([F:45])([F:44])[C:38]([C:40]([F:43])([F:42])[F:41])=[O:39]>C1COCC1>[F:36][C:37]([F:45])([F:44])[C:38]([C:2]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][C:3]=1[CH2:4][CH:5]1[CH2:13][C:12]2[C:7](=[CH:8][C:9]([O:20][CH3:21])=[C:10]([N:14]3[CH2:19][CH2:18][O:17][CH2:16][CH2:15]3)[CH:11]=2)[C:6]1=[O:22])([OH:39])[C:40]([F:43])([F:42])[F:41]

Participants

5

Reactant 3

HCID 12695HexafluoroacetoneHCID 117940114HCID 117940114, compoundHCID 178418339Butyllithium

Product 1

HCID 117940104HCID 117940104, compoundYield 15.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 2-(2-chloro-5-(trifluoromethyl)benzyl)-6-methoxy-5-morpholino-2,3-dihydro-1H-inden-1-one 269 (0.1 g, 0.226 mmol) in dry THF, cooled to 0° C., n-BuLi (0.021 g, 0.339 mmol) was added drop wise and the solution stirred for 10 min. Then hexafluoroacetone 244 (0.10 g, 0.453 mmol) was added to the reaction and stirred for another 2 h. After completion of the reaction, it was quenched with saturated ammonium chloride solution. The organic layer was separated and aqueous phase was extracted again with diethyl ether, the combined organic layer was dried over sodium sulphate and concentrated to get the crude 270, which was purified through 100-200 mesh silica gel by eluting with 15% ethyl acetate in hexane to give 20 mg of compound 2-(2-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-5-(trifluoromethyl)benzyl)-6-methoxy-5-morpholino-2,3-dihydro-1H-inden-1-one 270.

Workup

  1. stirringstirred for another 2 h
  2. customAfter completion of the reaction, it
  3. customwas quenched with saturated ammonium chloride solution
  4. customThe organic layer was separated
  5. extractionaqueous phase was extracted again with diethyl ether
  6. dry with materialthe combined organic layer was dried over sodium sulphate
  7. concentrationconcentrated
  8. customto get the crude 270, which
  9. customwas purified through 100-200 mesh silica gel
  10. washby eluting with 15% ethyl acetate in hexane

Sources & evidence

ORD record
ord-6da5e030de30477c8c3ab5e2c929e595
Source dataset
uspto-grants-2016_09
Patent number
US09446047B2

Reaction notes

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