Potassium Carbonate → Ethyl 2-(1-(tert-butoxycarbonyl)indolin-6-yl)thiazole-4-carboxylate

HRID 2178251Notes

Reaction equation

HRID 2178251 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH:17]=[C:16]3[C:12]([CH2:13][CH2:14][N:15]3[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[CH:11][CH:10]=2)O1.Br[C:27]1[S:28][CH:29]=[C:30]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[N:31]=1.C([O-])([O-])=O.[K+].[K+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:21]([O:20][C:18]([N:15]1[C:16]2[C:12](=[CH:11][CH:10]=[C:9]([C:27]3[S:28][CH:29]=[C:30]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[N:31]=3)[CH:17]=2)[CH2:13][CH2:14]1)=[O:19])([CH3:22])([CH3:23])[CH3:24]

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 353965Ethyl 2-bromo-1,3-thiazole-4-carboxylateHCID 59418722tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate

Product 1

HCID 59418726Ethyl 2-(1-(tert-butoxycarbonyl)indolin-6-yl)thiazole-4-carboxylateYield 61.4%

Reagents, catalysts & solvents 4

HCID 74236Tetrabutylammonium BromideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline-1-carboxylate (288) (69 mg, 0.2 mmol), ethyl 2-bromothiazole-4-carboxylate (43 mg, 0.2 mmol), K2CO3 (69 mg, 0.5 mmol), tetrabutylammonium bromide (6.0 mg, 0.02 mmol) and dichlorobis(triphenylphosphine)palladium(II) (6.0 mg, 0.003 mmol) in 1,4-dioxane (6 mL) and water (1 mL) was heated to 90° C. for 24 hours. After cooling the mixture was extracted into DCM, washed with H2O, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel eluting with a gradient of PE/EtOAc (9:1), to provide 46 mg (61%) of the desired product ethyl 2-(1-(tert-butoxycarbonyl)indolin-6-yl)thiazole-4-carboxylate (28C): 1H NMR (300 MHz, CDCl3) δ 8.13 (1H, s), 7.18 (1H, dd), 6.95 (1H, dd), 6.43 (1H, dd), 4.44 (2H, m), 3.99 (2H, m), 3.11 (1H, t), 2.97 (1H, t), 1.54 (9H, s), 1.45 (3H, t). LC/MS (APCI): m/z 375.0 (M+H).

Workup

  1. temperatureAfter cooling the mixture
  2. extractionwas extracted into DCM
  3. washwashed with H2O
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude material was purified by column chromatography on silica gel eluting with a gradient of PE/EtOAc (9:1)

Sources & evidence

ORD record
ord-2ca4893b42874bd9ae5ae0de16111a1e
Source dataset
uspto-grants-2015_06
Patent number
US09067928B2

Reaction notes

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