Dichloromethane → (2-(Tert-butoxy)-4-(4-(trifluoromethoxy)benzyl)quinolin-6-yl)(4-chlorophenyl)(thiazol-2-yl)methanol

HRID 1778297Notes

Reaction equation

HRID 1778297 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)([C:14]3[S:15][CH:16]=[CH:17][N:18]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH:3]=1.CC1(C)C(C)(C)OB([CH2:39][C:40]2[CH:45]=[CH:44][C:43]([O:46][C:47]([F:50])([F:49])[F:48])=[CH:42][CH:41]=2)O1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:27]([O:26][C:4]1[CH:3]=[C:2]([CH2:39][C:40]2[CH:45]=[CH:44][C:43]([O:46][C:47]([F:48])([F:49])[F:50])=[CH:42][CH:41]=2)[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)([C:14]3[S:15][CH:16]=[CH:17][N:18]=3)[OH:13])[CH:10]=2)[N:5]=1)([CH3:30])([CH3:29])[CH3:28]

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 162181464,4,5,5-Tetramethyl-2-(4-(trifluoromethoxy)benzyl)-1,3,2-dioxaborolaneHCID 118324020(4-Bromo-2-tert-butoxyquinolin-6-yl)(4-chlorophenyl)(thiazol-2-yl)methanol

Product 1

HCID 118323950(2-(Tert-butoxy)-4-(4-(trifluoromethoxy)benzyl)quinolin-6-yl)(4-chlorophenyl)(thiazol-2-yl)methanol

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of (4-bromo-2-(tert-butoxy)quinolin-6-yl)(4-chlorophenyl)(thiazol-2-yl)methanol (79 mg, 0.157 mmol) and 4,4,5,5-tetramethyl-2-(4-(trifluoromethoxy)benzyl)-1,3,2-dioxaborolane (80.5 mg, 0.267 mmol) in the presence of Pd(dppf)Cl2.CH2Cl2 (512 mg, 0.0157 mmol), Na2CO3 (33 mg, 0.314 mmol) in 1,4-dioxane (1 mL) and water (0.25 mL) was heated at 80° C. overnight. The reaction was diluted with EtOAc and water. The organics were concentrated and purified by silica column (80% EtOAc/hexanes) chromatography to yield (2-(tert-butoxy)-4-(4-(trifluoromethoxy)benzyl)quinolin-6-yl)(4-chlorophenyl)(thiazol-2-yl)methanol.

Workup

  1. concentrationThe organics were concentrated
  2. custompurified by silica column (80% EtOAc/hexanes) chromatography

Sources & evidence

ORD record
ord-3932325178c84490b74b82576e1ed4e6
Source dataset
uspto-grants-2016_02
Patent number
US09266835B2

Reaction notes

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