Dimethylformamide → HCID 22219969, compound

HRID 1794076Notes

Reaction equation

HRID 1794076 reaction equation
Cl[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.[H-].[Na+].[Cl:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH2:17][OH:18].CN(C=O)C>C1(C)C=CC=CC=1.O>[Cl:13][C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH2:17][O:18][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 701173-Chlorobenzyl alcoholHCID 792226-Chloronicotinic acid

Product 1

HCID 22219969HCID 22219969, compoundYield 142.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

6-chloronicotinic acid (1.0 g, 6.3 mmol)) was added portion-wise over 30 min to a stirred suspension of sodium hydride (60%, 0.76 g, 19 mmol) in toluene (10 mL. The mixture was stirred for 30 min then cooled to 0° C. A solution of 3-chloro-benzyl alcohol (0.69 g, 6.4 mmol) in toluene (5 mL) was added drop-wise over 10 min. The mixture was warmed to room temperature, DMF (20 mL) was added and the mixture was heated to 95° C. and stirred for 18 h. The mixture was cooled to room temperature then poured into water (30 mL). The aqueous mixture was acidified to pH 2 and extracted with ethyl acetate (2×30 mL). The combined organic extracts were washed with water and brine, then dried over sodium sulfate and concentrated in vacuo to give a yellow solid (2.36 g). The residue was re-crystallised [2-propanol-water, (2:1)] to give the product as a white solid (0.85 g, 51%), m.p. 158° C. (dec.). 1H-NMR (400 MHz, CDCl3): 8.93 (1H, d, J=2.5 Hz), 8.24 (1H, dd, J=2.5, 8.5 Hz), 7.46 (1H, s), 7.35–7.29 (3H, m), 6.87 (1H, dd, J=1, 8.5 Hz) and 5.45 (2H, s).

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. temperaturethe mixture was heated to 95° C.
  3. stirringstirred for 18 h
  4. temperatureThe mixture was cooled to room temperature
  5. extractionextracted with ethyl acetate (2×30 mL)
  6. washThe combined organic extracts were washed with water and brine
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-dd11367f04d042a9ab629541e39c8407
Source dataset
uspto-grants-2006_04
Patent number
US07022707B2

Reaction notes

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