Diethanolamine → (R)-2h [PMID:19625189]

HRID 1170922Notes

Reaction equation

HRID 1170922 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:10]([C@H:24]([CH3:32])[CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:11](=[O:23])[C:12]2[C:18]([C:19]([F:22])([F:21])[F:20])=[N:17][CH:16]=[CH:15][C:13]=2[N:14]=1.B(Cl)(Cl)Cl.N(CCO)CCO>ClCCl>[OH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[N:10]([C@H:24]([CH3:32])[CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:11](=[O:23])[C:12]2[C:18]([C:19]([F:22])([F:21])[F:20])=[N:17][CH:16]=[CH:15][C:13]=2[N:14]=1

Participants

5

Reactant 3

HCID 8113DiethanolamineHCID 25135Boron TrichlorideHCID 59553889(R)-2-(2-methoxyphenyl)-3-(1-phenylpropan-2-yl)-5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one

Product 1

HCID 135948915(R)-2h [PMID:19625189]Yield 65.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

(R)-2-(2-methoxyphenyl)-3-(1-phenylpropan-2-yl)-5-(trifluoromethyl)pyrido[4,3-d]pyrimidin-4(3H)-one (6.6 g, 15.02 mmol) was dissolved in anhydrous dichloromethane (75 mL) and cooled to 0° C. in an ice bath. To this was added a 1M dichloromethane solution of boron trichloride (31.5 mL, 31.5 mmol) slowly to maintain temperature. After addition, the reaction mixture was stirred for 2-5 minutes. The reaction mixture was transferred via canulla to a 0° C. aqueous solution of diethanolamine (10.3 g, 97.6 mmol in 150 mL water) with stirring. The reaction mixture was allowed to come to room temperature and stir for 1 hour. The reaction mixture was diluted with dichloromethane, and the layers separated. The organic layer was washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to provide a foam. This foam was purified by silica gel column chromatography using 20-40% ethyl acetate/hexanes as eluant to give a colorless foam which was then crystallized from ethyl acetate/hexanes to provide the product (4.2 g). 1H NMR (400 MHz, CDCl3) δ 8.79 (d, 1H), 7.6 (d, 1H), 7.45 (m, 1H), 7.00 (m, 6H), 6.90 (m, 2H), 3.60 (m, 2H), 3.10 (m, 2H), 1.99 (t, 3H). MS m/z 426.3 (M+H)+.

Workup

  1. temperatureto maintain temperature
  2. additionAfter addition
  3. customwas transferred via canulla to a 0° C.
  4. stirringwith stirring
  5. customto come to room temperature
  6. stirringstir for 1 hour
  7. customthe layers separated
  8. washThe organic layer was washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto provide a foam
  13. customThis foam was purified by silica gel column chromatography
  14. customto give a colorless foam which
  15. customwas then crystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-b4c74ed271f5402f8889c9b43d1ba5c8
Source dataset
uspto-grants-2010_11
Patent number
US07829572B2

Reaction notes

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