Sodium Hydroxide → (S)-4-(2-chloro-6-(5-fluoropyridin-3-yl)pyrimidin-4-yl)-3-methylmorpholine

HRID 1771526Notes

Reaction equation

HRID 1771526 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12](S(C)(=O)=O)[N:11]=[C:10]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][C@@H:19]3[CH3:24])[CH:9]=2)[CH:5]=[N:6][CH:7]=1.[OH-].[Na+].P(Cl)(Cl)([Cl:29])=O>>[Cl:29][C:12]1[N:11]=[C:10]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][C@@H:19]2[CH3:24])[CH:9]=[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([F:1])[CH:3]=2)[N:13]=1

Participants

4

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 86691144(S)-4-(6-(5-fluoropyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl)-3-methylmorpholine2×

Product 1

HCID 86691143(S)-4-(2-chloro-6-(5-fluoropyridin-3-yl)pyrimidin-4-yl)-3-methylmorpholine

Procedure

(S)-4-(6-(5-fluoropyridin-3-yl)-2-(methylsulfonyl)pyrimidin-4-yl)-3-methylmorpholine (intermediate 6) (132 mg, 0.19 mmol) was heated in phosphorus oxychloride (8 mL) overnight at 95° C. The reaction mixture was allowed to cool to room temperature and then portion wise added to ice water (100 mL) and left to stir for 1 hour. Carefully, NaOH pellets were added to basify the mixture. The resulting aqueous layer was extracted with DCM (100 mL), passed through a PTFE hydrophobic frit and the solvent removed in vacuo to yield a brown gum (110 mg) used without further purification.

Workup

  1. waitleft
  2. extractionThe resulting aqueous layer was extracted with DCM (100 mL)
  3. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-5d0b8e4253764350a93a170a4282d5af
Source dataset
uspto-grants-2016_02
Patent number
US09249129B2

Reaction notes

Loading…