反应详情

LiOH—H2O (6.58 g, 157 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 for 10 minutes, and then warmed to room temperature. LC/MS looked the same at 3 hours and 4.5 hours. The reaction mixture was cooled to 0° C., and then saturated NH4Cl was added to the mixture. The 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 the product was eluting, then ethyl acetate was flushed through the column. Then 30:1 DCM:MeOH eluted the rest of the product (8.83 g). The mixed fractions were re-flashed with Biotage 40 M using the same conditions to give another portion (2.99 g), which gave 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 foam. LC/MS (APCI+) m/z 335.1 [M+H]+.

1. customsame at 3 hours
2. custom4.5 hours
3. temperatureThe reaction mixture was cooled to 0° C.
4. stirringThe mixture was stirred for 5 minutes
5. custommost of the THF was removed by rotary evaporation
6. extractionThe mixture was extracted with EtOAc (3×250 mL)
7. dry with materialthe combined extracts were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. washOnce the product was eluting
11. customethyl acetate was flushed through the column
12. washThen 30:1 DCM:MeOH eluted the rest of the product (8.83 g)
13. customto give another portion (2.99 g), which