Methane → 7-Benzyl-4-chloro-2-(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-D]pyrimidine

HRID 1454804Notes

Reaction equation

HRID 1454804 reaction equation
[C:1]1([CH2:7][N:8]2[CH2:17][CH2:16][C:15]3[C:14](O)=[N:13][C:12]([C:19]([F:22])([F:21])[F:20])=[N:11][C:10]=3[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1(P(Cl)([Cl:31])=O)C=CC=CC=1.C(=O)(O)[O-].[Na+].C>CCCCCC.C(OCC)(=O)C>[Cl:31][C:14]1[C:15]2[CH2:16][CH2:17][N:8]([CH2:7][C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH2:9][C:10]=2[N:11]=[C:12]([C:19]([F:22])([F:21])[F:20])[N:13]=1

Participants

7

Reactant 4

HCID 297MethaneHCID 69990Phenylphosphonic dichlorideHCID 516892Sodium BicarbonateHCID 178517783HCID 178517783, compound

Product 1

HCID 184565217-Benzyl-4-chloro-2-(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-D]pyrimidine

Reagents, catalysts & solvents 2

HCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 29.6 g (95.7 mmol) of 7-(phenylmethyl)-2-(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-ol and 53 mL of phenylphosphonic dichloride in a 250-mL round bottom flask was heated at 150° C. After 2 h, the mixture was cooled to ambient temperature and poured onto 400 g of ice, transferring with about 500 mL of ethyl acetate. The aqueous layer was neutralized with solid sodium bicarbonate and the layers separated. The aqueous layer was extracted with two portions of ethyl acetate. The combined organics were washed sequentially with saturated aqueous sodium bicarbonate solution and brine, dried over sodium sulfate and concentrated to give a brown solid. The solid was boiled in 2 L of hexane with charcoal, filtered, and concentrated in vacuo to give the title compound as a yellow solid. LC-MS 328.3 (M+1).

Workup

  1. temperaturethe mixture was cooled to ambient temperature
  2. customthe layers separated
  3. extractionThe aqueous layer was extracted with two portions of ethyl acetate
  4. washThe combined organics were washed sequentially with saturated aqueous sodium bicarbonate solution and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customto give a brown solid
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-2f3182416ed046b1b7f7d0fe4f29afa9
Source dataset
uspto-grants-2009_01
Patent number
US07482336B2

Reaction notes

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