Water → HCID 90031906, compound

HRID 1048717Notes

Reaction equation

HRID 1048717 reaction equation
[F:1][C:2]([F:33])([F:32])[C:3]1[CH:4]=[C:5]([C:9]#[C:10][C:11]2[N:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]3=[N:13][C:12]=2[CH2:20][O:21][C:22]2[CH:31]=[CH:30][CH:29]=[CH:28][C:23]=2[C:24](OC)=[O:25])[CH:6]=[CH:7][CH:8]=1.COCCO[AlH2-]OCCOC.[Na+].O.[OH-].[Na+]>O1CCCC1.C(OCC)(=O)C>[F:33][C:2]([F:1])([F:32])[C:3]1[CH:4]=[C:5]([C:9]#[C:10][C:11]2[N:15]3[CH:16]=[CH:17][CH:18]=[CH:19][C:14]3=[N:13][C:12]=2[CH2:20][O:21][C:22]2[CH:31]=[CH:30][CH:29]=[CH:28][C:23]=2[CH2:24][OH:25])[CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 16684438Red-AlHCID 73051808HCID 73051808, compound

Product 1

HCID 90031906HCID 90031906, compoundYield 61.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

In a flask placed under an argon flow, 0.16 g (0.352 mmol) of methyl 2-((3-((3-(trifluoromethyl)-phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl)methoxy)benzoate were dissolved in 4 ml of tetrahydrofurane with magnetic stirring, the mixture was cooled to 0° C. and then 0.148 ml (0.492 mmol) of RED-Al were added. The mixture was stirred at 0° C. for 15 min before being diluted with 15 ml of ethyl acetate and poured into 20 ml of water. With intense stirring, 1 ml of a NaOH aqueous solution (32% by mass) was slowly added. After separation, the organic phase was washed with 2×10 ml of water. The aqueous phases were extracted with 2×5 ml of ethyl acetate. The combined organic phases were washed with 20 ml of a saturated NaCl aqueous solution and then dried on Na2SO4 which was then removed by filtration. The obtained filtrate was concentrated in vacuo. The crude residue was purified by trituration in 10 ml of diisopropyl ether. The solid was isolated by filtration and dried in vacuo. 0.091 g (yield=58%) of (2-((3-((3-(trifluoromethyl)phenyl)ethynyl)imidazo[1,2-a]pyridin-2-yl) methoxy)phenyl)methanol were obtained as a pale brown solid. LC-MS: m/z=425 (M+2H+); UV purity at 254 nm=94%. 1H NMR (300 MHz, DMSO) δ 8.77 (d, J=6.8 Hz, 1H), 8.05 (s, 1H), 7.92 (d, J=7.6 Hz, 1H), 7.73 (dt, J=14.3, 7.8 Hz, 3H), 7.55-7.43 (m, 1H), 7.38 (d, J=7.4 Hz, 1H), 7.20 (d, J=3.6 Hz, 3H), 7.03-6.86 (m, 1H), 5.39 (s, 2H), 4.98 (t, J=5.7 Hz, 1H), 4.55 (d, J=5.6 Hz, 2H).

Workup

  1. customIn a flask placed under an argon
  2. customAfter separation
  3. washthe organic phase was washed with 2×10 ml of water
  4. extractionThe aqueous phases were extracted with 2×5 ml of ethyl acetate
  5. washThe combined organic phases were washed with 20 ml of a saturated NaCl aqueous solution
  6. customdried on Na2SO4 which
  7. customwas then removed by filtration
  8. concentrationThe obtained filtrate was concentrated in vacuo
  9. customThe crude residue was purified by trituration in 10 ml of diisopropyl ether
  10. customThe solid was isolated by filtration
  11. customdried in vacuo

Sources & evidence

ORD record
ord-13c2570f4e6647de8a6ffa8b241596e1
Source dataset
uspto-grants-2016_07
Patent number
US09381191B2

Reaction notes

Loading…