Methanol → (E)-6-amino-2-cyclopropyl-5-(2-(trimethylsilyl)vinyl)pyrimidine-4-carboxylic acid

HRID 244313Notes

Reaction equation

HRID 244313 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[N:5]=[C:4]([C:11]([O:13]CC)=[O:12])[C:3]=1/[CH:16]=[CH:17]/[Si:18]([CH3:21])([CH3:20])[CH3:19].CO.O.O.[OH-].[Li+]>C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[N:5]=[C:4]([C:11]([OH:13])=[O:12])[C:3]=1/[CH:16]=[CH:17]/[Si:18]([CH3:19])([CH3:21])[CH3:20]

Participants

6

Reactant 4

HCID 887MethanolHCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 68150547HCID 68150547, compound

Product 1

HCID 70497238(E)-6-amino-2-cyclopropyl-5-(2-(trimethylsilyl)vinyl)pyrimidine-4-carboxylic acidYield 17.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(E)-ethyl 6-amino-2-cyclopropyl-5-(2-(trimethylsilyl)vinyl)pyrimidine-4-carboxylate (0.666 g, 2.180 mmol) was dissolved in THF (8.7 mL), MeOH (8.7 mL), and Water (4.4 mL). Lithium hydroxide hydrate (0.274 g, 6.54 mmol) was added as a solid. The reaction mixture was stirred for 15 min at room temperature. The solvent was removed under vacuum. The resulting solid was partitioned between 1 N HCl and ethyl acetate. The aqueous phase was extracted with ethyl acetate three times. The combined organics were washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated. The solid was triturated with hexane (15 mL) and gently heated with heat gun. The solid from the resulting suspension was collected via filtration and dried under vaccum to provide the title compound as an off-white solid (0.104 g, 17% yield): mp 146-149° C.; 1H NMR (400 MHz, DMSO-d6) δ 0.12 (s, 9H), 0.91-1.03 (m, 4H), 2.02 (tt, J=7.8, 5.1 Hz, 1H), 6.22 (d, J=19.3 Hz, 1H), 6.74 (d, J=19.3 Hz, 1H), 7.34 (s, 2H); ESIMS m/z 278 ([M+H]+), 276 ([M−H]−)

Workup

  1. customThe solvent was removed under vacuum
  2. customThe resulting solid was partitioned between 1 N HCl and ethyl acetate
  3. extractionThe aqueous phase was extracted with ethyl acetate three times
  4. washThe combined organics were washed with saturated sodium chloride
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe solid was triturated with hexane (15 mL)
  9. temperaturegently heated
  10. temperaturewith heat gun
  11. filtrationThe solid from the resulting suspension was collected via filtration
  12. customdried under vaccum

Sources & evidence

ORD record
ord-b0f9a8f9f98a45489e106350cbdb5dba
Source dataset
uspto-grants-2014_02
Patent number
US08658568B2

Reaction notes

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