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

HRID 423659Notes

Reaction equation

HRID 423659 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]([OH:16])=[N:14][CH:15]=1.CS(O[C@@H:22]([CH:24]1[CH2:29][CH2:28][N:27]([C:30]([O:32][CH:33]([CH3:35])[CH3:34])=[O:31])[CH2:26][CH2:25]1)[CH3:23])(=O)=O.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[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:22]([CH:24]2[CH2:25][CH2:26][N:27]([C:30]([O:32][CH:33]([CH3:34])[CH3:35])=[O:31])[CH2:28][CH2:29]2)[CH3:23])=[N:14][CH:15]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 866387501-Methylethyl 4-{(1R)-1-[(methylsulfonyl)oxy]ethyl}-1-piperidinecarboxylateHCID 178503116HCID 178503116, compound

Product 1

HCID 666731611-Methylethyl 4-[(1S)-1-({5-[2-fluoro-4-(methylthio)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylateYield 45%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-Methylethyl 4-[(1S)-1-({5-[2-fluoro-4-(methylthio)phenyl]-2-pyrazinyl}oxy)ethyl]-1-piperidinecarboxylate (0.334 g, 45%) was prepared as a yellow oil from 5-[2-fluoro-4-(methylthio)phenyl]-2-pyrazinol (and tautomers thereof) (prepared as in Example 161, Alternative synthesis, Step 4, 0.405 g, 1.71 mmol), crude 1-methylethyl 4-{(1R)-1-[(methylsulfonyl)oxy]ethyl}-1-piperidinecarboxylate (0.70 g, 2.32 mmol) and K2CO3 (0.48 g, 3.43 mmol) in DMF (15 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 25% EtOAc/hexanes. 1H NMR (400 MHz, CDCl3): δ 8.52 (s, 1H), 8.22 (d, 1H, J=1.3 Hz), 7.85 (t, 1H, J=8.3 Hz), 7.10 (dd, 1H, Ja=8.3 Hz, Jb=1.7 Hz), 7.01 (dd, 1H, Ja=12.1 Hz, Jb=1.8 Hz), 5.15-5.05 (m, 1H), 4.89 (septet, 1H, J=6.2 Hz), 4.19 (bs, 2H), 2.80-2.65 (m, 2H), 2.50 (s, 3H), 1.85-1.65 (m, 3H), 1.40-1.15 (m, 11H); LRMS (ESI), m/z 434 (M+H).

Workup

  1. customThe crude product was purified by chromatography on an ISCO silica gel column

Sources & evidence

ORD record
ord-b2586d5a63bc416887b177d539b96e14
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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