反应详情

LiOH—H2O (6.577 g, 156.7 mmol) was added to a 0° C. solution of (5R)-tert-butyl 4-(7-acetoxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (23.6 g, 62.69 mmol) in 2:1 THF:H2O (320 mL). The reaction mixture was stirred 10 minutes and then warmed to room temperature. LC/MS looked same at 3 and 4.5 hours. The reaction mixture was cooled to 0° C., and saturated NH4Cl was added. The reaction mixture was stirred for 5 minutes, and most of the THF was removed by rotary evaporation. The mixture was extracted with EtOAc (3×250 mL), and the combined extracts were dried (Na2SO4), filtered, and concentrated. The crude was flashed on Biotage 65M: 4:1 DCM:ethyl acetate, then gradient to 1:1 to 1:4 DCM:ethyl acetate. Once product eluting, then ethyl acetate flushed through column, then 30:1 DCM:MeOH eluted rest of product (8.83 g), mixed fractions re-flashed with Biotage 40M using same conditions to give another 2.99 g which give a combined yield of (5R)-tert-butyl 4-(7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (11.82 g, 56.38% yield) as a brown foam. LC/MS (APCI+) m/z 335.1 [M+H]+.

1. customlooked same at 3 and 4.5 hours
2. temperatureThe reaction mixture was cooled to 0° C.
3. stirringThe reaction mixture was stirred for 5 minutes
4. custommost of the THF was removed by rotary evaporation
5. extractionThe mixture was extracted with EtOAc (3×250 mL)
6. dry with materialthe combined extracts were dried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated
9. washOnce product eluting
10. customethyl acetate flushed through column
11. addition30:1 DCM:MeOH eluted rest of product (8.83 g), mixed fractions
12. customto give another 2.99 g which