Ethyl Acetate → (4-((2-Amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)-3-methoxyphenyl)methanol

HRID 2387808Notes

Reaction equation

HRID 2387808 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]2[CH:19]=[CH:18][C:13]([C:14](OC)=[O:15])=[CH:12][C:11]=2[O:20][CH3:21])=[C:4]([NH:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[N:3]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-].CCOC(C)=O.[OH-].[Na+]>C1COCC1>[NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH2:9][C:10]2[CH:19]=[CH:18][C:13]([CH2:14][OH:15])=[CH:12][C:11]=2[O:20][CH3:21])=[C:4]([NH:22][CH2:23][CH2:24][CH2:25][CH2:26][CH3:27])[N:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 49806175Methyl 4-((2-amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)-3-methoxybenzoate

Product 1

HCID 66819929(4-((2-Amino-4-methyl-6-(pentylamino)pyrimidin-5-yl)methyl)-3-methoxyphenyl)methanolYield 42.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of the product from step (iv) (2.4 g) in THF (50 mL) was added portionwise over 10 min to a stirred solution of lithium aluminum hydride (1M in THF; 12.89 mL) in THF (50 mL) at 0° C. under nitrogen. The resulting mixture was stirred at 0° C. for 10 min and then at rt for 1 h. EtOAc (20 mL) was added portionwise over 10 min and the resulting mixture stirred for a further 20 min. The mixture was added portionwise to 2M NaOH (300 mL) and stirred for 30 min. The resulting suspension was filtered through a pad of celite and the resulting biphasic filtrate separated. The aqueous phase was extracted with EtOAc (200 mL) and the combined organic phase was dried, filtered and evaporated. The crude product was purified by chromatography, eluting with 5 to 10% MeOH in DCM. to afford the subtitle compound as a colorless gum 0.94 g.

Workup

  1. waitat rt for 1 h
  2. stirringthe resulting mixture stirred for a further 20 min
  3. stirringstirred for 30 min
  4. filtrationThe resulting suspension was filtered through a pad of celite
  5. customthe resulting biphasic filtrate separated
  6. extractionThe aqueous phase was extracted with EtOAc (200 mL)
  7. customthe combined organic phase was dried
  8. filtrationfiltered
  9. customevaporated
  10. customThe crude product was purified by chromatography
  11. washeluting with 5 to 10% MeOH in DCM

Sources & evidence

ORD record
ord-3dcbd00489ff48499d1b3320799fc471
Source dataset
uspto-grants-2012_09
Patent number
US08268990B2

Reaction notes

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