Water → 4-[2-(4-Methanesulfonyl-phenyl)-furo[2,3-b]pyrazin-6-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1184690Notes

Reaction equation

HRID 1184690 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[O:23][C:17]3=[N:18][CH:19]=[C:20](Cl)[N:21]=[C:16]3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][S:25]([C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)(=[O:27])=[O:26].C([O-])([O-])=O.[Na+].[Na+].O>CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[O:23][C:17]3=[N:18][CH:19]=[C:20]([C:31]4[CH:32]=[CH:33][C:28]([S:25]([CH3:24])(=[O:27])=[O:26])=[CH:29][CH:30]=4)[N:21]=[C:16]3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 866748844-(2-Chloro-furo[2,3-b]pyrazin-6-yl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 679735514-[2-(4-Methanesulfonyl-phenyl)-furo[2,3-b]pyrazin-6-yl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-(2-chloro-furo[2,3-b]pyrazin-6-yl)-piperidine-1-carboxylic acid tert-butyl ester (200 mg), 4-(methanesulfonyl)phenyl boronic acid (140 mg), Na2CO3 (126 mg), water (2.5 mL), and N,N-dimethylformamide (2.5 mL) is sparged with argon for 10 min and Pd(PPh3)4 (15 mg) is added. The resulting mixture is stirred at 100° C. for 1.5 h. After cooling to room temperature, water and ethyl acetate are added. The organic phase is washed with brine, dried (MgSO4), and the solvent is evaporated. The residue is chromatographed on silica gel (ethyl acetate/cyclohexane 60:40) to give an oily residue that is triturated with diethyl ether and dried to afford the title compound as a colorless solid. Yield: 175 mg (65% of theory); LC (method 2): tR=1.35 min; Mass spectrum (ESI+): m/z=458 [M+H]+.

Workup

  1. customis sparged with argon for 10 min
  2. additionPd(PPh3)4 (15 mg) is added
  3. temperatureAfter cooling to room temperature
  4. additionwater and ethyl acetate are added
  5. washThe organic phase is washed with brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent is evaporated
  8. customThe residue is chromatographed on silica gel (ethyl acetate/cyclohexane 60:40)
  9. customto give an oily residue that
  10. customis triturated with diethyl ether
  11. customdried

Sources & evidence

ORD record
ord-18d4ad3d05de475396f3d3cdecc27ffa
Source dataset
uspto-grants-2014_03
Patent number
US08669271B2

Reaction notes

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