Acetaldehyde → HCID 58497968, compound

HRID 1505258Notes

Reaction equation

HRID 1505258 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15](=[O:40])[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH2:26][C:25]([C:31]3[CH:36]=[C:35]([Cl:37])[CH:34]=[C:33]([Cl:38])[CH:32]=3)([C:27]([F:30])([F:29])[F:28])[O:24][N:23]=2)=[CH:18][C:17]=1[CH3:39].[CH:41](=[O:43])[CH3:42]>O1CCCC1>[CH3:13][O:14][C:15](=[O:40])[C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:26]([CH:41]([OH:43])[CH3:42])[C:25]([C:31]3[CH:32]=[C:33]([Cl:38])[CH:34]=[C:35]([Cl:37])[CH:36]=3)([C:27]([F:30])([F:28])[F:29])[O:24][N:23]=2)=[CH:18][C:17]=1[CH3:39]

Participants

6

Reactant 4

HCID 177AcetaldehydeHCID 7912DiisopropylamineHCID 59563501Methyl 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoateHCID 178418339Butyllithium

Product 1

HCID 58497968HCID 58497968, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of N,N-diisopropylamine (0.24 ml) in dry tetrahydrofuran (6 ml) stirred under argon at 0° C., was added butyl lithium (2.5M in hexane) (0.80 ml). The solution was stirred at 0° C. for 30 minutes then was cooled to −85° C. To this solution was added a solution of 4-[5-(3,5-dichloro-phenyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester (preparation described in, for example, EP 1,731,512) (404 mg) in dry tetrahydrofuran (3 ml). The reaction mixture was stirred at −85° C. until deprotonation was completed as monitored by thin layer chromatography. Then, to this solution was added acetaldehyde (0.14 ml) and the reaction mixture was stirred at −85° C. for 1.5 hours. The reaction was quenched by addition of aqueous ammonium chloride (saturated) at −85° C. The mixture allowed to warm to ambient temperature and was then extracted with dichloromethane. The combined organic extracts were dried over magnesium sulfate and concentrated. The residue was purified by chromatography on silica gel (eluent: heptane/diethyl ether 60:40) to give 4-[5-(3,5-dichloro-phenyl)-4-(1-hydroxy-ethyl)-5-trifluoromethyl-4,5-dihydro-isoxazol-3-yl]-2-methyl-benzoic acid methyl ester (290 mg) as a white solid. 1H-NMR (CDCl3, 400 MHz): 7.98-7.96 (d, 1H), 7.60-7.45 (m, 5H), 4.09-4.08 (m, 1H), 3.96-3.91 (m, 1H), 3.91 (s, 3H), 2.63 (s, 3H), 1.07 and 0.94 (d, 3H).

Workup

  1. temperaturethen was cooled to −85° C
  2. stirringThe reaction mixture was stirred at −85° C. until deprotonation
  3. stirringthe reaction mixture was stirred at −85° C. for 1.5 hours
  4. customThe reaction was quenched by addition of aqueous ammonium chloride (saturated) at −85° C
  5. temperatureto warm to ambient temperature
  6. extractionwas then extracted with dichloromethane
  7. dry with materialThe combined organic extracts were dried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by chromatography on silica gel (eluent: heptane/diethyl ether 60:40)

Sources & evidence

ORD record
ord-b3b31340e28b47a7b2b231db73d1ad69
Source dataset
uspto-grants-2015_12
Patent number
US09216973B2

Reaction notes

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