Diisopropylamine → HCID 71544234, compound

HRID 2205537Notes

Reaction equation

HRID 2205537 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.[Cl:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[S:21][CH:22]=[CH:23][N:24]=2)=[CH:16][CH:15]=1.[N:25]1[CH:30]=[CH:29][C:28]([C:31](=[O:33])[CH3:32])=[CH:27][CH:26]=1>C1COCC1>[Cl:13][C:14]1[CH:15]=[CH:16][C:17]([C:20]2[S:21][C:22]([C:31]([C:28]3[CH:29]=[CH:30][N:25]=[CH:26][CH:27]=3)([OH:33])[CH3:32])=[CH:23][N:24]=2)=[CH:18][CH:19]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 142824-AcetylpyridineHCID 13215562HCID 13215562, compoundHCID 178418339Butyllithium

Product 1

HCID 71544234HCID 71544234, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of diisopropylamine (0.2 mL, 1.538 mmol) in dry THF (5 mL), was added 1.6M n-BuLi in hexanes (0.96 mL, 1.538 mmol) slowly at −78° C. The reaction mixture was stirred for 30 min, 2-(4-chlorophenyl)thiazole (0.2 g, 1.025 mmol) in THF (10.0 mL) added, the mixture stirred for 30 min, a solution of 1-(pyridin-4-yl)ethanone (0.17 mL, 1.538 mmol) in THF (5.0 mL) added, and the mixture was stirred for 2 hours at −78° C. The reaction mixture was quenched with saturated NH4Cl (50 mL) solution and extracted with EtOAc (2×100 mL). The organic layer was washed with water (2×50 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to obtain crude product. The crude product was purified by column chromatography (1% methanol in dichloromethane) to obtain 1-(2-(4-chlorophenyl)thiazol-5-yl)-1-(pyridin-4-yl)ethanol as off-white solid (0.1 g, 31% yield) in 99.9% HPLC purity. 1H NMR (400 MHz, DMSO-d6): δ 8.51 (d, 2H), 7.87 (d, 2H), 7.82 (s, 1H), 7.51-7.47 (m, 4H), 6.66 (s, 1H), 1.92 (s, 3H); LC-MS m/z calculated for [M+H]+317.04. found 317.4.

Workup

  1. stirringthe mixture stirred for 30 min
  2. stirringthe mixture was stirred for 2 hours at −78° C
  3. customThe reaction mixture was quenched with saturated NH4Cl (50 mL) solution
  4. extractionextracted with EtOAc (2×100 mL)
  5. washThe organic layer was washed with water (2×50 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customto obtain crude product
  10. customThe crude product was purified by column chromatography (1% methanol in dichloromethane)

Sources & evidence

ORD record
ord-b4d151531d84475cb6d2ff87fbd8e078
Source dataset
uspto-grants-2016_06
Patent number
US09371316B2

Reaction notes

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