Reaction #1654

Reaction equation

methanol

product

(R)-9-(2,3-Dihydro-2-furanyl)-9H-purin-6-amine

trimethylacetylchloride

methylene chloride methanol

→

(R)-N-[9-(2,3-Dihydro-2-furanyl)-9H-purin-6-yl]-2,2-dimethylpropanamide

Yield 94.0%

Solvents

pyridine

Conditions

Workup

1. 1
   OtherA slight 3° C. exotherm
2. 2
   TemperatureThe reaction solution was cooled to 25° C.
3. 3
   Concentrationconcentrated in vacuo to a thick orange syrup
4. 4
   workup.DISSOLUTIONThe residue was dissolved in methylene chloride (1.5 liters)
5. 5
   Washwashed with 0.5N sodium bisulfate (3×500 mL), 1N sodium bisulfate (2×500 mL)
6. 6
   Extractionextracted with methylene chloride (1×500 mL)
7. 7
   Dryingdried over anhydrous sodium sulfate
8. 8
   Filtrationfiltered
9. 9
   Concentrationconcentrated in vacuo to a light orange oil
10. 10
    Concentrationconcentrated in vacuo

Procedure

To a suspension of the product of Step C (196 g, 0.97 mole), 4-dimethylaminopyridine (5.9 g, 0.048 mole) in dry pyridine (970 mL) at 26° C. was added dropwise over 1 hr trimethylacetylchloride (145 mL, 142.1 g, 1.18 mole, 1.2 equiv.). A slight 3° C. exotherm was noted. The reaction mixture was then heated to 55° C. for 4 hr becoming a pale yellow-orange solution. Analysis by TLC (methylene chloride:methanol (90:10), Rf (product) 0.75) showed the reaction was complete. The reaction solution was cooled to 25° C. and methanol (40 mL) was slowly added. The reaction solution was then stirred for 30 min, then concentrated in vacuo to a thick orange syrup. The residue was dissolved in methylene chloride (1.5 liters) and washed with 0.5N sodium bisulfate (3×500 mL), 1N sodium bisulfate (2×500 mL), then brine (1×500 mL). All aqueous washes were combined and extracted with methylene chloride (1×500 mL). All methylene chloride extracts were combined and dried over anhydrous sodium sulfate, then filtered and concentrated in vacuo to a light orange oil. The oil was suspended in toluene (200 mL) and concentrated in vacuo. The product solidified to a pale yellow solid weighing 262 g for a yield of 94%.

Source