Ethyl Acetate → (R)-4-(1-(4-bromophenyl)-2,2,2-trifluoroethoxy)-6-chloropyrimidin-2-amine

HRID 1499252Notes

Reaction equation

HRID 1499252 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([OH:13])[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.[Cl:14][C:15]1[CH:20]=[C:19](Cl)[N:18]=[C:17]([NH2:22])[N:16]=1.C([O-])([O-])=O.[Cs+].[Cs+].CCOC(C)=O>O1CCOCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([O:13][C:19]2[CH:20]=[C:15]([Cl:14])[N:16]=[C:17]([NH2:22])[N:18]=2)[C:9]([F:11])([F:12])[F:10])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 655222-Amino-4,6-dichloropyrimidineHCID 12640349(1R)-1-(4-Bromophenyl)-2,2,2-trifluoroethan-1-ol

Product 1

HCID 117942299(R)-4-(1-(4-bromophenyl)-2,2,2-trifluoroethoxy)-6-chloropyrimidin-2-amine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (R)-1-(4-bromophenyl)-2,2,2-trifluoroethanol (150 mg, 0.60 mmol) in dioxane (10 mL) was added 4,6-dichloropyrimidin-2-amine (120 mg g, 0.71 mmol) and Cs2CO3 (290 mg, 0.88 mmol), and the reaction mixture was heated to 80° C. for 30 h. Then the reaction was cooled to RT. EtOAc was added and the organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by normal phase silica gel column (EtOAc/heptane) provided (R)-4-(1-(4-bromophenyl)-2,2,2-trifluoroethoxy)-6-chloropyrimidin-2-amine as a colorless oil.

Workup

  1. temperatureThen the reaction was cooled to RT
  2. washthe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification by normal phase silica gel column (EtOAc/heptane)

Sources & evidence

ORD record
ord-3bdff7d4df424030ac938cea3010f7ba
Source dataset
uspto-grants-2015_12
Patent number
US09199994B2

Reaction notes

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