Water → 4-[3-Chloro-4-(3,3,3-trifluoro-2-hydroxy-1-methyl-2-quinolin-3-yl-propyl)-phenoxymethyl]-benzoic acid ethyl ester

HRID 1095960Notes

Reaction equation

HRID 1095960 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:26])[CH:5]=[CH:6][C:7]=1[CH:8]([CH3:25])[C:9]([OH:24])([C:14]1[CH:15]=[N:16][C:17]2[C:22]([CH:23]=1)=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:10]([F:13])([F:12])[F:11].[H-].[Na+].[CH2:29]([O:31][C:32](=[O:41])[C:33]1[CH:38]=[CH:37][C:36]([CH2:39]Br)=[CH:35][CH:34]=1)[CH3:30].O>CN(C)C(=O)C.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:29]([O:31][C:32](=[O:41])[C:33]1[CH:38]=[CH:37][C:36]([CH2:39][O:26][C:4]2[CH:5]=[CH:6][C:7]([CH:8]([CH3:25])[C:9]([OH:24])([C:14]3[CH:15]=[N:16][C:17]4[C:22]([CH:23]=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)[C:10]([F:11])([F:13])[F:12])=[C:2]([Cl:1])[CH:3]=2)=[CH:35][CH:34]=1)[CH3:30]

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydride2×HCID 954261Ethyl 4-(bromomethyl)benzoate2×HCID 574212993-Chloro-4-(3,3,3-trifluoro-2-hydroxy-1-methyl-2-quinolin-3-yl-propyl)-phenol

Product 1

HCID 666990254-[3-Chloro-4-(3,3,3-trifluoro-2-hydroxy-1-methyl-2-quinolin-3-yl-propyl)-phenoxymethyl]-benzoic acid ethyl esterYield 41.3%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 3-chloro-4-(3,3,3-trifluoro-2-hydroxy-1-methyl-2-quinolin-3-yl-propyl)-phenol (68 mg) in N,N-dimethylacetamide (1 ml) was added NaH (55% dispersion in mineral oil, 8.5 mg) at 0° C. The mixture was stirred at 0° C. for 1 h and at room temperature for 1 h. Ethyl-4-(bromomethyl)benzoate (48 mg) was added and the mixture was stirred overnight. Since the reaction was not finished, tetrabutylammonium iodide (6.5 mg) and NaH (55% dispersion in mineral oil, 8.5 mg) were added and the mixture was stirred overnight at room temperature and for 2 h at 50° C. Ethyl-4-(bromomethyl)benzoate (4 mg) was added and the mixture was stirred for 2 h at 50° C. The reaction mixture was poured into water and extracted with EtOAc. The organic phase was washed with water and brine, dried (MgSO4), filtered and concentrated. The product was purified by chromatography (SiO2, cyclohexane=>cyclohexane/EtOAc 1:1) to give the title compound (40 mg) as an orange solid. MS (m/e)=543.8 [M+H+].

Workup

  1. stirringthe mixture was stirred overnight
  2. stirringthe mixture was stirred overnight at room temperature and for 2 h at 50° C
  3. stirringthe mixture was stirred for 2 h at 50° C
  4. extractionextracted with EtOAc
  5. washThe organic phase was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe product was purified by chromatography (SiO2, cyclohexane=>cyclohexane/EtOAc 1:1)

Sources & evidence

ORD record
ord-039bdf7907fc4e4b8240408d715d3dd4
Source dataset
uspto-grants-2012_03
Patent number
US08138189B2

Reaction notes

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