Hydrochloric Acid → R-112

HRID 71352Notes

Reaction equation

HRID 71352 reaction equation
Cl[C:2]1[N:7]=[C:6](Cl)[C:5]([F:9])=[CH:4][N:3]=1.[NH2:10][C:11]1[CH:12]=[C:13]([OH:17])[CH:14]=[CH:15][CH:16]=1.Cl>CO.O>[OH:17][C:13]1[CH:12]=[C:11]([NH:10][C:2]2[N:7]=[C:6]([NH:10][C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=3)[C:5]([F:9])=[CH:4][N:3]=2)[CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 115683-AminophenolHCID 2507052,4-Dichloro-5-fluoropyrimidine

Product 1

HCID 9904854R-112

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent2×

Procedure

A mixture of 2,4-dichloro-5-fluoropyrimidine (0.0167 g, 0.1 mmol) and 3-aminophenol (0.033 g, 0.3 mmol) in MeOH: H2O (1.8:0.2 mL; v/v) was shaken in a sealed tube at 100° C. for 24 h (or 80° C. for 3 days), cooled to room temperature, diluted with water (15 mL), acidified with 2N HCl (pH>2). Upon saturation with sodium chloride it was extracted with ethyl acetate (3×20 mL), dried over anhydrous sodium sulfate and solvent was removed. The resulting residue was filtered through a pad of silica gel (200-400 mesh) using CH2Cl2->1>10% MeOH in CH2Cl2 to obtain the desired N2,N4-bis(3-hydroxyphenyl)-5-fluoro-2,4-pyrimidinediamine (R921218). If the reaction scale is large enough, solid of the resulting product can be isolated by filtration. 1H NMR (CDCl3): δ 7.73 (d, 1H, J=5.1 Hz), 7.12-6.90 (m, 6H), 6.64 (dd, 1H, J=1.8 and 8.1 Hz), 6.53 (dd, 1H, J=1.2 and 5.7 Hz); LCMS: ret. time: 16.12 min.; purity: 100%; MS (m/e): 313 (MH+).

Workup

  1. extractionUpon saturation with sodium chloride it was extracted with ethyl acetate (3×20 mL)
  2. dry with materialdried over anhydrous sodium sulfate and solvent
  3. customwas removed
  4. filtrationThe resulting residue was filtered through a pad of silica gel (200-400 mesh)

Sources & evidence

ORD record
ord-5abbf685b9df42328f96e38717e6069a
Source dataset
uspto-grants-2014_09
Patent number
US08822685B2

Reaction notes

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