Potassium Carbonate → HCID 14074268, compound

HRID 1723029Notes

Reaction equation

HRID 1723029 reaction equation
Br.Br.[OH:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)=[CH:6][CH:5]=1.Cl[CH2:17][C:18]1[CH:23]=[C:22]([O:24][CH3:25])[N:21]=[C:20]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[N:19]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[OH:3][C:4]1[CH:5]=[CH:6][C:7]([N:10]2[CH2:15][CH2:14][N:13]([CH2:17][C:18]3[CH:23]=[C:22]([O:24][CH3:25])[N:21]=[C:20]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[N:19]=3)[CH2:12][CH2:11]2)=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 11430Potassium Carbonate3×HCID 2723591p-(1-Piperazinyl)phenol dihydrobromideHCID 20026486HCID 20026486, compound

Product 1

HCID 14074268HCID 14074268, compoundYield 58.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4.94 g (14.5 mmol) of 1-(4-hydroxyphenyl)piperazine dihydrobromide, 3.29 g (14 mmol) of 4-chloromethyl-6-methoxy-2-phenylpyrimidine and 2.00 g (14.5 mmol) of powdered potassium carbonate in 50 ml of absolute N,N-dimethylformamide (DMF) was warmed to 80° C., and 322 mg of powdered K2CO3 were added with stirring under a nitrogen atmosphere in each case after 10 minutes, after a further 25 minutes, and after a further 60 minutes (total addition of 966 mg (7 mmol) of K2CO3). The mixture was stirred for a further 2.5 hours at 80° C., the DMF was substantially removed by distillation in an oil-pump vacuum in a rotary evaporator, the crystalline residue was mixed with 40 ml of water and 50 ml of CH2Cl2, the pH of the mixture was adjusted to 5-6 using 2N HCl, the phases were separated, and the aqueous phase was extracted three times with CH2Cl2. The combined CH2Cl2 extracts were dried, filtered and evaporated in vacuo. The residue (4.25 g) was chromatographed on a silica gel S/CH2Cl2 column (diameter 2.0 cm, height 23 cm) by elution with CH2Cl2 and CH2Cl2 /C2H5OH mixtures, with increasing C2H5OH content (to a maximum of 4% by volume of C2H5OH). The fractions which were unary according to TLC were combined and crystallized from CH3OH. In this fashion 3.06 g (=58% yield) of 4-(4-hydroxyphenyl)-1-(6-methoxy-2-phenylpyrimidin-4-yl-methyl)piperazine were obtained; melting point 166°-67° C., analysis: C22H24N4O2 (MW 376.46) calc. C 70.19, H 6.43, N 14.88; found C 69.9, H 6.4, N 14.5%.

Workup

  1. stirringThe mixture was stirred for a further 2.5 hours at 80° C.
  2. customthe DMF was substantially removed by distillation in an oil-pump vacuum in a rotary evaporator
  3. additionthe crystalline residue was mixed with 40 ml of water and 50 ml of CH2Cl2
  4. customthe phases were separated
  5. extractionthe aqueous phase was extracted three times with CH2Cl2
  6. dry with materialThe combined CH2Cl2 extracts were dried
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue (4.25 g) was chromatographed on a silica gel S/CH2Cl2 column (diameter 2.0 cm, height 23 cm) by elution with CH2Cl2 and CH2Cl2 /C2H5OH mixtures, with increasing C2H5OH content (to a maximum of 4% by volume of C2H5OH)
  10. customcrystallized from CH3OH

Sources & evidence

ORD record
ord-c77caa5f2c8746b582e815c00f8e7356
Source dataset
uspto-grants-1989_08
Patent number
US04859670

Reaction notes

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