반응 #160932

반응 방정식

NaOH

methyl 6-((R)-3-hydroxypyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinate

→

title compound

6-((R)-3-Hydroxypyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinic acid

용매

MeOH

반응 조건

후처리

1. 1
   기타The MeOH was evaporated off under reduced pressure
2. 2
   workup.ADDITIONthe aq. residue was treated with brine (90 mL)
3. 3
   추출extracted with MeTHF twice (540 mL+360 mL)
4. 4
   세척the combined organic layers were washed with water (90 mL)
5. 5
   workup.ADDITIONMeTHF was added to the combined aq. layers
6. 6
   온도the biphasic mixture was cooled to 0° C.
7. 7
   추출extracted with MeTHF
8. 8
   세척The combined organic extracts were washed with brine
9. 9
   기타the solvent was evaporated off under reduced pressure
10. 10
    기타to give a residue which
11. 11
    기타was recrystallized from a EtOAc/TBME (1:1)

실험 절차

Aq. NaOH (180 mL of 2.6 M) was added to a solution of methyl 6-((R)-3-hydroxypyrrolidin-1-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinate (Stage 9.5, 111 g, 299 mmol) in MeOH (270 mL) and the RM was stirred at RT for 14 h. The MeOH was evaporated off under reduced pressure and the aq. residue was treated with brine (90 mL), extracted with MeTHF twice (540 mL+360 mL) and the combined organic layers were washed with water (90 mL). MeTHF was added to the combined aq. layers, the biphasic mixture was cooled to 0° C. and acidified (pH=4-4.5) with aq. HCl solution (18%) and extracted with MeTHF. The combined organic extracts were washed with brine and the solvent was evaporated off under reduced pressure to give a residue which was recrystallized from a EtOAc/TBME (1:1) to afford the title compound as a white solid. HPLC (Condition 7) tR=4.74 min, LC-MS (Condition 8) tR=3.37 min, m/z=359.0 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.44 (br. s, 2H), 1.51 (d, J=11.54 Hz, 2H), 1.64-1.86 (m, 4H), 1.90 (br. s, 1H), 2.31 (d, J=9.29 Hz, 1H), 2.77 (br. s, 1H), 3.10 (br. s, 1H), 3.21 (d, J=8.78 Hz, 2H), 3.27-3.51 (m, 4H), 3.87 (d, J=11.54 Hz, 1H), 4.16 (br. s, 1H), 4.75-4.93 (m, 1H), 5.04 (br. s, 1H), 6.35 (d, J=17.32 Hz, 1H), 7.51-7.64 (m, 1H), 7.64-7.82 (m, 1H), 8.67 (d, J=2.26 Hz, 1H), 12.58 (br. s, 1H).

출처