Sodium Carbonate → 4-[5-(4-Methanesulfonylphenyl)furo[2,3-c]pyridin-2-yl]piperidine-1-carboxylic acid tert-butyl ester

HRID 1471773Notes

Reaction equation

HRID 1471773 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=[CH:18][N:19]=[C:20](Cl)[CH: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+]>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[O:23][C:17]3=[CH:18][N: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)[CH:21]=[C:16]3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27343644-(Methanesulfonyl)phenylboronic acidHCID 866748894-(5-Chlorofuro[2,3-c]pyridin-2-yl)piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 679736224-[5-(4-Methanesulfonylphenyl)furo[2,3-c]pyridin-2-yl]piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
170 °C

Procedure

A mixture of 4-(5-chloro-furo[2,3-c]pyridin-2-yl)-piperidine-1-carboxylic acid tert-butyl ester (390 mg), 4-(methanesulfonyl)phenyl boronic acid (350 mg), 2 M aqueous Na2CO3 solution (1.50 mL), and 1,4-dioxane (10 mL) is sparged with Ar for 10 min. Pd(PPh3)4 (100 mg) is added and the resulting mixture is stirred at 170° C. for 1 h in a microwave oven. The reaction mixture is concentrated, diluted with water, and extracted with ethyl acetate. The combined extracts are washed with brine, dried (MgSO4), and concentrated. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 60:40→40:60) to give the title compound. LC (method 2): tR=1.23 min; Mass spectrum (ESI+): m/z=457 [M+H]+.

Workup

  1. customis sparged with Ar for 10 min
  2. additionPd(PPh3)4 (100 mg) is added
  3. concentrationThe reaction mixture is concentrated
  4. additiondiluted with water
  5. extractionextracted with ethyl acetate
  6. washThe combined extracts are washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue is chromatographed on silica gel (cyclohexane/ethyl acetate 60:40→40:60)

Sources & evidence

ORD record
ord-d8cfb2cc21ed4a3985927d06794aa49b
Source dataset
uspto-grants-2015_04
Patent number
US09012456B2

Reaction notes

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