Water → 1-Methylethyl 4-[(1S)-1-({5-[2-fluoro-4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate

HRID 423660Notes

Reaction equation

HRID 423660 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]1[N:11]=[CH:12][C:13]([O:16][C@H:17]([CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][CH:28]([CH3:30])[CH3:29])=[O:26])[CH2:21][CH2:20]2)[CH3:18])=[N:14][CH:15]=1.[OH:31]OS([O-])=O.[K+].[OH2:37]>CC(C)=O>[F:1][C:2]1[CH:7]=[C:6]([S:8]([CH3:9])(=[O:31])=[O:37])[CH:5]=[CH:4][C:3]=1[C:10]1[N:11]=[CH:12][C:13]([O:16][C@H:17]([CH:19]2[CH2:20][CH2:21][N:22]([C:25]([O:27][CH:28]([CH3:30])[CH3:29])=[O:26])[CH2:23][CH2:24]2)[CH3:18])=[N:14][CH:15]=1

Participants

5

Reactant 3

HCID 962WaterHCID 23707502Potassium hydroxy sulfiteHCID 666731611-Methylethyl 4-[(1S)-1-({5-[2-fluoro-4-(methylthio)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate

Product 1

HCID 249958961-Methylethyl 4-[(1S)-1-({5-[2-fluoro-4-(methylsulfonyl)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

The title compound (0.195 g) was prepared from 1-methylethyl 4-[(1S)-1-({5-[2-fluoro-4-(methylthio)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate (0.33 g, 0.76 mmol) and Oxone® (1.41 g, 2.29 mmol) in acetone (25 mL) and water (10 mL) in a manner similar to Example 166, Step 2. The crude product was purified by chromatography on an ISCO silica gel column using 0 to 50% EtOAc/hexanes, followed by chiral separation on an AS-H column with 25% MeOH in CO2, 140 bar, 40° C. at 2 mL/min. The first eluting peak was further purified by trituration with 9% EtOAc/hexanes to afford the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.64 (s, 1H), 8.27 (s, 1H), 8.20 (t, 1H, J=7.8 Hz), 7.85-7.70 (m, 2H), 5.20-5.10 (m, 1H), 4.89 (septet, 1H, J=6.2 Hz), 4.30-4.15 (m, 2H), 3.09 (s, 3H), 2.80-2.65 (m, 2H), 1.90-1.65 (m, 3H), 1.40-1.15 (m, 11H); LRMS (ESI), m/z 466 (M+H).

Workup

  1. customThe crude product was purified by chromatography on an ISCO silica gel column
  2. customfollowed by chiral separation on an AS-H column with 25% MeOH in CO2, 140 bar, 40° C. at 2 mL/min
  3. customThe first eluting peak was further purified by trituration with 9% EtOAc/hexanes

Sources & evidence

ORD record
ord-3e724bd1095c4a1ea17b3745cfcceda1
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

Loading…