Triethylamine → Benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-carbamate

HRID 604204Notes

Reaction equation

HRID 604204 reaction equation
[F:1][C:2]([F:23])([F:22])[C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1)[CH2:6][NH:7][C:8]1[N:13]=[CH:12][C:11]([Br:14])=[CH:10][N:9]=1.C(N([CH2:29][CH3:30])CC)C.Cl[C:32](Cl)([O:34][C:35](=[O:41])OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[F:23][C:2]([F:1])([F:22])[C:3]1[CH:4]=[C:5]([CH:15]=[C:16]([C:18]([F:21])([F:20])[F:19])[CH:17]=1)[CH2:6][N:7]([C:8]1[N:13]=[CH:12][C:11]([Br:14])=[CH:10][N:9]=1)[C:35](=[O:41])[O:34][CH2:32][C:30]1[CH:29]=[CH:16][CH:17]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 57551007(3,5-Bis-trifluoromethyl-benzyl)-(5-bromopyrimidin-2-yl)-amine

Product 1

HCID 86626518Benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-carbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amine (10 g) and triethylamine (4.18 ml) are dissolved in methylene chloride (100 mL) and thereto is added triphosgene (2.97 g) under ice-cooling. The reaction solution is stirred at the same temperature for 30 minutes and concentrated under reduced pressure. The resulting residue is dissolved in tetrahydrofuran (100 mL) and thereto are added benzyl alcohol (3.88 ml) and triethylamine (10.45 ml) at room temperature and the mixture is stirred overnight. The reaction solution is diluted with ethyl acetate and washed with a saturated aqueous sodium bicarbonate solution and a 1N-hydrochloric acid. The organic layer is washed with a saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=97:3→9:1) to give benzyl (3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-carbamate (11.58 g). MS (m/z): 534/536 [M+H]+

Workup

  1. temperaturecooling
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe resulting residue is dissolved in tetrahydrofuran (100 mL)
  4. additionare added benzyl alcohol (3.88 ml) and triethylamine (10.45 ml) at room temperature
  5. stirringthe mixture is stirred overnight
  6. additionThe reaction solution is diluted with ethyl acetate
  7. washwashed with a saturated aqueous sodium bicarbonate solution
  8. washThe organic layer is washed with a saturated brine
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=97:3→9:1)

Sources & evidence

ORD record
ord-71b7fc27ba8342e5bb6e3c5af96c8725
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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