Methanol → (2-Anilinopyridin-3-yl)methanol

HRID 1769011Notes

Reaction equation

HRID 1769011 reaction equation
[C:1]1([NH:7][C:8]2[C:13]([C:14](O)=[O:15])=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.COB(OC)OC.B.CSC.CO>C1COCC1>[C:1]1([NH:7][C:8]2[C:13]([CH2:14][OH:15])=[CH:12][CH:11]=[CH:10][N:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 8470Trimethyl borateHCID 14817992-Anilinonicotinic acidHCID 12423031(Dimethyl sulfide)trihydroboron

Product 1

HCID 13986159(2-Anilinopyridin-3-yl)methanolYield 49.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a refluxing solution of 6.5 g (30.4 mmole) of 2-phenylamino-3-pyridinecarboxylic acid and 7.5 mL (64.2 mmoles) of trimethylborate in 40 mL of THF under N2 was added dropwise, 65 mL (130 mmole) of 2M borane-methyl sulfide over a 30 min period. The reaction mixture was refluxed for 2 hrs, then cooled, and 50 mL of CH3OH was added dropwise with stirring over a period of 30 min. The mixture was refluxed for 5 min, and the solvents were evaporated to leave a gummy light yellow semi-solid which was partitioned between 250 mL of 2N HCl and 150 mL of CH2Cl2. The aqueous layer was separated and brought to pH 8 (NaHCO3), and the mixture was extracted with CH2Cl2 (700 mL). The CH2Cl2 was evaporated to leave 3.0 g of semi-solid which was purified by dry-column chromatography (glass column, 4×60 cm; 235 gm of silica; eluted with CH2Cl2). The fractions containing the product were extracted with CH2Cl2 then with CH3OH. The solvents were evaporated, and the oily residue was converted to the HCl salt in acetone-Et2O to give 1.4 g (40%) of creamcolored solid; mp 180°-182° C. (J. Med. Chem. 11, 894 (1968), mp 189°-190° C.). MS (EI) m/e (relative intensity): 200 (M+, 27), 199 (24), 182 (65), 181 (100).

Workup

  1. temperatureThe reaction mixture was refluxed for 2 hrs
  2. temperaturecooled
  3. temperatureThe mixture was refluxed for 5 min
  4. customthe solvents were evaporated
  5. customto leave a gummy light yellow semi-solid which
  6. customwas partitioned between 250 mL of 2N HCl and 150 mL of CH2Cl2
  7. customThe aqueous layer was separated
  8. extractionthe mixture was extracted with CH2Cl2 (700 mL)
  9. customThe CH2Cl2 was evaporated

Sources & evidence

ORD record
ord-bdc0c588041f4c839a22ad7b105d22cf
Source dataset
uspto-grants-1995_01
Patent number
US05380734

Reaction notes

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