Ethanol → (4-Chloro-2-pyridin-3-yl-thiazol-5-yl)-ethyl-carbamic acid tert-butyl ester

HRID 2199227Notes

Reaction equation

HRID 2199227 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3](B(O)O)[CH:2]=1.C(O)C.C([O-])([O-])=O.[K+].[K+].[C:19]([O:23][C:24](=[O:35])[N:25]([C:28]1[S:32][C:31](Br)=[N:30][C:29]=1[Cl:34])[CH2:26][CH3:27])([CH3:22])([CH3:21])[CH3:20]>C1(C)C=CC=CC=1.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:19]([O:23][C:24](=[O:35])[N:25]([C:28]1[S:32][C:31]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)=[N:30][C:29]=1[Cl:34])[CH2:26][CH3:27])([CH3:20])([CH3:21])[CH3:22]

Participants

8

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 59580445HCID 59580445, compound

Product 1

HCID 59580483(4-Chloro-2-pyridin-3-yl-thiazol-5-yl)-ethyl-carbamic acid tert-butyl esterYield 79.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of 3-pyridine boronic acid (1.5 g, 12.2 mmol) in toluene (50 mL) was added absolute ethanol (25 mL) followed by a 2.0 M solution of K2CO3 (12.5 mL). To this mixture was added (2-bromo-4-chloro-thiazol-5-yl)-ethyl-carbamic acid tert-butyl ester (4.2 g, 12.2 mmol) followed by tetrakis(triphenylphosphine)palladium(0) (708 mg, 0.61 mmol). The reaction mixture was heated to 100° C. for 16 h. The mixture was cooled and diluted with ethyl acetate. The organic layer was washed with saturated aqueous NaHCO3, dried over Na2SO4, filtered and concentrated. The organic layer was purified by silica gel chromatography (0 to 100% ethyl acetate/hexanes) to afford a red oil (3.3 g, 79%): 1H NMR (300 MHz, CDCl3) δ 9.09 (d, J=1.9 Hz, 1H), 8.68 (dd, J=4.8, 1.6 Hz, 1H), 8.19 (dd, J=5.9, 4.2 Hz, 1H), 7.39 (dd, J=7.6, 5.2 Hz, 1H), 3.68 (q, J=7.2 Hz, 2H), 1.45 (s, 9H), 1.22 (t, J=7.0 Hz, 3H); ESIMS m/z 340 (M+1).

Workup

  1. temperatureThe mixture was cooled
  2. washThe organic layer was washed with saturated aqueous NaHCO3
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe organic layer was purified by silica gel chromatography (0 to 100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f5fbd6d570484fc3a2237e18c260ff41
Source dataset
uspto-grants-2016_06
Patent number
US09357780B2

Reaction notes

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