Dichloromethane → 2-(6-Methylpyridin-3-yl)thiazole-5-carbaldehyde

HRID 57411Notes

Reaction equation

HRID 57411 reaction equation
Br[C:2]1[S:3][C:4]([CH:7]=[O:8])=[CH:5][N:6]=1.[CH3:9][C:10]1[N:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:9][C:10]1[N:15]=[CH:14][C:13]([C:2]2[S:3][C:4]([CH:7]=[O:8])=[CH:5][N:6]=2)=[CH:12][CH:11]=1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 27630812-Methylpyridine-5-boronic acidHCID 27732592-Bromo-1,3-thiazole-5-carbaldehyde

Product 1

HCID 904167222-(6-Methylpyridin-3-yl)thiazole-5-carbaldehydeYield 41.4%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-bromothiazole-5-carbaldehyde (400 mg, 2.08 mmol), (6-methylpyridin-3-yl)boronic acid (428 mg, 3.12 mmol, 1.5 equiv), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (170 mg, 0.21 mmol, 0.1 equiv) and 2.0 M aqueous sodium carbonate (5.2 mL, 10.4 mmol, 5 equiv) in 1,2-dimethoxyethane (6.9 mL) was heated in a microwave reactor at 110° C. for 20 minutes. The reaction was then diluted with ethyl acetate (50 mL) and water (50 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (30 mL), dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc) provided 2-(6-methylpyridin-3-yl)thiazole-5-carbaldehyde (0.176 g, brown solid) in 41% yield. 1H NMR (400 MHz, CDCl3) δ 10.08 (s, 1H), 9.15 (d, J=2.0 Hz, 1H), 8.47 (s, 1H), 8.19 (dd, J=8.1, 2.4 Hz, 1H), 7.31 (d, J=8.3 Hz, 1H), 2.66 (s, 3H). MS m/z 205.0 (M+H)+; Rt-0.36 min.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with ethyl acetate (2×25 mL)
  3. washThe combined organic extracts were washed with saturated aqueous sodium chloride (30 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-422e222764954d9e8d60bf5455a56031
Source dataset
uspto-grants-2016_09
Patent number
US09434719B2

Reaction notes

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