Sodium Carbonate → Tert-butyl 4-((2-chloro-5-(4-methoxyphenyl)pyridin-4-ylamino)methyl)-4-fluoropiperidine-1-carboxylate

HRID 384704Notes

Reaction equation

HRID 384704 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[Cl:7][C:8]1[CH:13]=[C:12]([NH:14][CH2:15][C:16]2([F:29])[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[C:11](I)=[CH:10][N:9]=1.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC#N>[Cl:7][C:8]1[CH:13]=[C:12]([NH:14][CH2:15][C:16]2([F:29])[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[C:11]([C:36]2[CH:37]=[CH:38][C:33]([O:32][CH3:31])=[CH:34][CH:35]=2)=[CH:10][N:9]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 59613359Tert-butyl 4-((2-chloro-5-iodopyridin-4-ylamino)methyl)-4-fluoropiperidine-1-carboxylate

Product 1

HCID 59613485Tert-butyl 4-((2-chloro-5-(4-methoxyphenyl)pyridin-4-ylamino)methyl)-4-fluoropiperidine-1-carboxylateYield 48.1%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
100 °C

Procedure

MeCN (0.72 mL) and 0.5M aqueous sodium carbonate (0.24 mL, 1.5 eq.) were added to a mixture of tert-butyl 4-((2-chloro-5-iodopyridin-4-ylamino)methyl)-4-fluoropiperidine-1-carboxylate (37 mg, 0.079 mmol), 4-methoxyphenylboronic acid (11.97 mg, 0.079 mmol), and tetrakis(triphenylphosphine) palladium(0) (4.55 mg, 3.94 μmol) in a 0.5 mL microwave reaction vial. The sealed vial was heated at 100° C. for 20 mins by microwave irradiation. The volatiles were removed in vacuo. The residue was dissolved in dichloromethane and loaded onto a 12+S Biotage silica column. Chromatography, eluting with a gradient of EtOAc in hexanes, gave tert-butyl 4-((2-chloro-5-(4-methoxyphenyl)pyridin-4-ylamino)methyl)-4-fluoropiperidine-1-carboxylate (17 mg, 0.038 mmol, 48%) as a colourless solid.

Workup

  1. customThe volatiles were removed in vacuo
  2. dissolutionThe residue was dissolved in dichloromethane
  3. washChromatography, eluting with a gradient of EtOAc in hexanes

Sources & evidence

ORD record
ord-57557d5cb92e49f4b97442175d49ab7b
Source dataset
uspto-grants-2013_02
Patent number
US08367658B2

Reaction notes

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