Acetic Acid → HCID 68693569, compound

HRID 2236450Notes

Reaction equation

HRID 2236450 reaction equation
[CH3:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:3]=1.[C:17](=O)([O:20]C)[O:18][CH3:19].[Li+].CC([N-]C(C)C)C.CC(O)=O>C1COCC1>[CH3:19][O:18][C:17]([CH2:1][C:2]1[C:7]([C:8]([OH:10])=[O:9])=[CH:6][N:5]=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:3]=1)=[O:20]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 12021Dimethyl CarbonateHCID 2399754-methyl-2-phenylpyrimidine-5-carboxylic acidHCID 2724682Lithium diisopropylamide

Product 1

HCID 68693569HCID 68693569, compoundYield 89.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
25 °C

Procedure

A solution of 3.00 g (14.0 mmol) of 4-Methyl-2-phenyl-pyrimidine-5-carboxylic Acid and 2.53 g (28.0 mmol) of dimethyl carbonate in 75 mL of THF is added dropwise with rapid overhead stirring to a slurry of 6.00 g (56.1 mmol) of LDA in 24 mL of THF at −78° C. The mixture is stirred at 25° C. for 5 h and then chilled to −78° C. The reaction is added all at once and rapidly (overhead stirring) to 81 mL (1.40 mol) of glacial HOAc in 210 mL of THF, also held at −78° C. The mixture is warmed to 25° C. and the THF and some HOAc is removed. Water (180 mL) is added and the product is extracted into EtOAc. The extract is washed with H2O (5×), dried (MgSO4) and evaporated. The residue is dissolved in excess aqueous NaHCO3 and extracted with Et2O (5×). These washes were discarded. The aqueous solution is acidified with 2M HCl and extracted with Et2O. The ethereal extracts were backwashed with H2O (6×), dried (MgSO4) and evaporated to give 3.4 g (89%) of orange crystals: mp 173-175° C. (dec); 1H NMR (DMSO-d6) δ 9.29 (s, 1H), 8.44 (m, 2H), 7.60 (m, 3H), 4.45 (s, 2H), 3.65 (s, 3H); MS (ESI) m/z 271.0 (M−H). Analysis for C14H12N2O: Calcd: C, 61.76; H, 4.44; N, 10.29. Found: C, 61.90; H, 4.73; N, 10.11.

Workup

  1. temperaturechilled to −78° C
  2. additionThe reaction is added all at once and
  3. customalso held at −78° C
  4. temperatureThe mixture is warmed to 25° C.
  5. customthe THF and some HOAc is removed
  6. additionWater (180 mL) is added
  7. extractionthe product is extracted into EtOAc
  8. washThe extract is washed with H2O (5×)
  9. dry with materialdried (MgSO4)
  10. customevaporated
  11. dissolutionThe residue is dissolved in excess aqueous NaHCO3
  12. extractionextracted with Et2O (5×)
  13. extractionextracted with Et2O
  14. dry with materialdried (MgSO4)
  15. customevaporated

Sources & evidence

ORD record
ord-88db0098ae804c48a9538546a2482b06
Source dataset
uspto-grants-2010_05
Patent number
US07713994B2

Reaction notes

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