반응 #534968

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4-Fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one

citric acid

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4-Fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one monocitrate

용매

Acetonitrile

반응 조건

후처리

1. 1
   기타a white slurry obtained
2. 2
   workup.DISSOLUTIONdissolution
3. 3
   온도with heating
4. 4
   온도The solid was cooled
5. 5
   기타isolated by vacuum filtration
6. 6
   세척washed with acetonitrile (10 vol. 5 ml)
7. 7
   기타The solid (1.0 g not dried)
8. 8
   workup.ADDITIONwas added
9. 9
   workup.STIRRINGThe slurry was stirred at ambient temperature overnight
10. 10
    기타The solid was isolated by vacuum filtration
11. 11
    세척washed with acetonitrile (10 vol, 5 ml)
12. 12
    기타The white solid was dried under vacuum at 60° C. for 25 hours

실험 절차

4-Fluoro-6-methyl-1-[1-(tetrahydro-2H-pyran-4-yl)-4-piperidinyl]-1,3-dihydro-2H-benzimidazol-2-one free base (1.499 mmol, 500 mg, 1 wt) was weighed into a 250 ml round bottomed flask, citric acid (1 eq, 1.499 mmol, 288 mg,) was added. Acetonitrile (95 vol. 47.5 ml) was added and a white slurry obtained, dissolution was not achieved with heating using a hot air gun. The slurry was magnetically stirred at 35° C. for four days under nitrogen. The solid was cooled and isolated by vacuum filtration and washed with acetonitrile (10 vol. 5 ml). The solid (1.0 g not dried) was recombined with the mother liquors plus acetonitrile (29 vol., 14.5 ml) and n-propanol (22 vol. 11 ml) was added. The slurry was stirred at ambient temperature overnight. The solid was isolated by vacuum filtration and washed with acetonitrile (10 vol, 5 ml). The white solid was dried under vacuum at 60° C. for 25 hours. 506 mg, 64%.

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