Benzyl Alcohol → Benzyl (2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-carbamate

HRID 604051Notes

Reaction equation

HRID 604051 reaction equation
[F:1][C:2]([F:37])([F:36])[C:3]1[CH:4]=[C:5]([CH:29]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:31]=1)[CH2:6][N:7]([CH2:15][C:16]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[CH:21][C:17]=1C(O)=O)[C:8]1[N:13]=[CH:12][C:11]([Br:14])=[CH:10][N:9]=1.O(P([N:54]=[N+]=[N-])(OC1C=CC=CC=1)=O)C1C=CC=CC=1.[CH2:57]([OH:64])[C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1.Cl.[O:66]1[CH2:70]CCC1>C(OCC)(=O)C.C(N(CC)CC)C>[F:35][C:32]([F:34])([F:33])[C:30]1[CH:29]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:37])[F:36])[CH:31]=1)[CH2:6][N:7]([CH2:15][C:16]1[CH:24]=[C:23]([C:25]([F:27])([F:26])[F:28])[CH:22]=[CH:21][C:17]=1[NH:54][C:70](=[O:66])[O:64][CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)[C:8]1[N:9]=[CH:10][C:11]([Br:14])=[CH:12][N:13]=1

Participants

8

Reactant 5

HCID 244Benzyl AlcoholHCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 123414Diphenylphosphoryl azideHCID 86626801HCID 86626801, compound

Product 1

HCID 86626807Benzyl (2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-carbamate

Reagents, catalysts & solvents 2

HCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

2-{[(3,5-Bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-benzoic acid (2.5 g) is dissolved in tetrahydrofuran (25 ml), and thereto are added diphenoxyphosphinylazide (1.34 ml), triethylamine (174 ml) and benzyl alcohol (1.3 ml) and the mixture is heated at 60° C. overnight with stirring. The reaction solution is cooled to room temperature, and thereto are added a 1N-hydrochloric acid and ethyl acetate, and the mixture is separated, and 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=1:0→9:1→4:1) to give benzyl (2-{[(3,5-bis-trifluoromethyl-benzyl)-(5-bromo-pyrimidin-2-yl)-amino]-methyl}-4-trifluoromethyl-phenyl)-carbamate (2.66 g). MS (m/z): 707/709 [M+H]+

Workup

  1. temperatureThe reaction solution is cooled to room temperature
  2. customthe mixture is separated
  3. washthe organic layer is washed with a saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=1:0→9:1→4:1)

Sources & evidence

ORD record
ord-2c83f9a628a540f2a65ef43c8fe4272a
Source dataset
uspto-grants-2011_03
Patent number
US07906517B2

Reaction notes

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