Boron tribromide → 4-(2-{(5-Ethylpyrimidin-2-yl)[4-(trifluoromethoxy)benzyl]amino}ethyl)-2-methylphenol

HRID 2251499Notes

Reaction equation

HRID 2251499 reaction equation
[CH2:1]([C:3]1[CH:4]=[N:5][C:6]([N:9]([CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([O:30]C)=[C:26]([CH3:32])[CH:25]=2)[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][C:18]([F:21])([F:20])[F:19])=[CH:13][CH:12]=2)=[N:7][CH:8]=1)[CH3:2].B(Br)(Br)Br.C[O-].[Na+]>ClCCl>[CH2:1]([C:3]1[CH:8]=[N:7][C:6]([N:9]([CH2:10][C:11]2[CH:12]=[CH:13][C:14]([O:17][C:18]([F:20])([F:21])[F:19])=[CH:15][CH:16]=2)[CH2:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([OH:30])=[C:26]([CH3:32])[CH:25]=2)=[N:5][CH:4]=1)[CH3:2]

Participants

5

Reactant 3

HCID 25134Boron tribromide2×HCID 10942334Sodium MethoxideHCID 690996425-ethyl-N-[2-(4-methoxy-3-methylphenyl)ethyl]-N-[4-(trifluoromethoxy)benzyl]pyrimidin-2-amine

Product 1

HCID 596433794-(2-{(5-Ethylpyrimidin-2-yl)[4-(trifluoromethoxy)benzyl]amino}ethyl)-2-methylphenol

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 5-ethyl-N-[2-(4-methoxy-3-methylphenyl)ethyl]-N-[4-(trifluoromethoxy)benzyl]pyrimidin-2-amine (1.12 g; 2.53 mmol) in dichloromethane (70 ml) was cooled in an ice bath and treated under nitrogen with boron tribromide (1M solution in dichloromethane; 2.78 ml). Allowed to warm to rt and additional boron tribromide (2.53 ml) was added. Stirred for 2 hr and concentrated. Azeotroped 3× with MeOH, redissolved in MeOH and treated with sodium methoxide (0.14 g; 2.53 mmol). Stirred for 30 minutes and concentrated. The residue was partitioned between ethyl acetate and water. The organic phase was dried over MgSO4, filtered and concentrated to afford 4-(2-{(5-ethylpyrimidin-2-yl)[4-(trifluoromethoxy)benzyl]amino}ethyl)-2-methylphenol as a dark brown oil (0.98 g; 90% crude yield) which was used in subsequent steps without further purification.

Workup

  1. concentrationconcentrated
  2. customAzeotroped 3× with MeOH
  3. dissolutionredissolved in MeOH
  4. stirringStirred for 30 minutes
  5. concentrationconcentrated
  6. customThe residue was partitioned between ethyl acetate and water
  7. dry with materialThe organic phase was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-4f99f7f69d004a16a07521f28718fe39
Source dataset
uspto-grants-2008_01
Patent number
US07319104B2

Reaction notes

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