Isopropanol → 6-[(Propan-2-yl)oxy]pyridine-3-carboxylic acid

HRID 1099426Notes

Reaction equation

HRID 1099426 reaction equation
CC(C)([O-:4])C.[K+].[CH:7]([OH:10])([CH3:9])[CH3:8].Cl[C:12]1C=CC(C#N)=[CH:14][N:13]=1.[O:20]1[CH2:24][CH2:23][CH2:22][CH2:21]1>>[CH:7]([O:10][C:12]1[CH:21]=[CH:22][C:23]([C:24]([OH:20])=[O:4])=[CH:14][N:13]=1)([CH3:9])[CH3:8]

Participants

5

Reactant 4

HCID 3776IsopropanolHCID 8028TetrahydrofuranHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 23665647Potassium tert-butoxide

Product 1

HCID 186257386-[(Propan-2-yl)oxy]pyridine-3-carboxylic acidYield 85%

Procedure

To a solution of potassium tert-butoxide (0.891 g, 7.94 mmol) in tetrahydrofuran (40 mL) at 0° C. was isopropanol (0.608 mL, 7.94 mmol) added. 6-chloronicotinonitrile (1.0 g, 7.22 mmol) was added after stirring for 5 min and the reaction mixture was allowed to reach ambient temperature. The reaction mixture was concentrated in vacuo, water (50 mL) was added and the resulting mixture extracted with ethyl acetate (3×50 mL). The crude was suspended in 4M sodium hydroxide (30 mL) and heated to reflux over night. The reaction mixture was concentrated in vacuo and 1M hydrochloric acid was added until an acidic pH was reached. The formed precipitate was collected by filtration and washed with water to yield 1.140 g (85%) of the title compound; 1H NMR (400 MHz, DMSO-d6) δ ppm 12.99 (s, 1 H), 8.70 (d, 1 H), 8.10 (dd, 1 H), 6.82 (d, 1 H), 5.21-5.40 (m, 1 H), 1.31 (d, 6 H); MS (ESI) m/z 182[M+H+].

Workup

  1. customat 0° C.
  2. additionadded
  3. customto reach ambient temperature
  4. concentrationThe reaction mixture was concentrated in vacuo, water (50 mL)
  5. additionwas added
  6. extractionthe resulting mixture extracted with ethyl acetate (3×50 mL)
  7. temperatureheated
  8. temperatureto reflux over night
  9. concentrationThe reaction mixture was concentrated in vacuo and 1M hydrochloric acid
  10. additionwas added until an acidic pH
  11. filtrationThe formed precipitate was collected by filtration
  12. washwashed with water

Sources & evidence

ORD record
ord-dae7ceadb6d649a7977e52e1f29df0b0
Source dataset
uspto-grants-2012_03
Patent number
US08143408B2

Reaction notes

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