Cesium carbonate → 3-[2-Chloro-4-(4-methanesulfonyl-benzyloxy)-phenyl]-1,1,1-trifluoro-2-quinolin-3-yl-butan-2-ol

HRID 333839Notes

Reaction equation

HRID 333839 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+].[CH3:29][S:30]([C:33]1[CH:40]=[CH:39][C:36]([CH2:37]Br)=[CH:35][CH:34]=1)(=[O:32])=[O:31].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([O:26][CH2:37][C:36]2[CH:35]=[CH:34][C:33]([S:30]([CH3:29])(=[O:32])=[O:31])=[CH:40][CH:39]=2)[CH:5]=[CH:6][C:7]=1[CH:8]([CH3:25])[C:9]([C:14]1[CH:15]=[N:16][C:17]2[C:22]([CH:23]=1)=[CH:21][CH:20]=[CH:19][CH:18]=2)([OH:24])[C:10]([F:11])([F:13])[F:12]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 24758Sodium hydrideHCID 27335814-(Methylsulfonyl)benzyl BromideHCID 574212993-Chloro-4-(3,3,3-trifluoro-2-hydroxy-1-methyl-2-quinolin-3-yl-propyl)-phenol

Product 1

HCID 574740523-[2-Chloro-4-(4-methanesulfonyl-benzyloxy)-phenyl]-1,1,1-trifluoro-2-quinolin-3-yl-butan-2-olYield 63.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 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 (Example 179, 75 mg) in N,N-dimethylacetamide (1 ml) was added NaH (60% dispersion in mineral oil, 9 mg) at 0° C. The mixture was stirred at 0° C. for 1 h and at room temperature for 1 h. 4-Methylsulfonylbenzyl bromide (54 mg) was added and the mixture was stirred at room temperature for 3 h. Cesium carbonate (32 mg) was added and the mixture was stirred for 2 days at room temperature and for 5 h at 50° C. The reaction mixture was poured into water and extracted with EtOAc. The organic phase was washed with brine and dried (MgSO4). The product was purified by chromatography (SiO2, cyclohexane=>cyclohexane/EtOAc 1:1) to give the title compound (69 mg) as a light yellow solid. MS (m/e)=550.3 [M+H+].

Workup

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

Sources & evidence

ORD record
ord-bd38c237e9df404f9bdcd5d288c80706
Source dataset
uspto-grants-2014_11
Patent number
US08883786B2

Reaction notes

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