Potassium Carbonate → methyl 4-(4-(5-(6-cyclopropylpyridin-3-yl)thiazol-2-yl)-tetrahydro-2H-pyran-4-yl)benzoate

HRID 415956Notes

Reaction equation

HRID 415956 reaction equation
[CH:1]1([C:4]2[CH:9]=[CH:8][C:7](B3OC(C)(C)C(C)(C)O3)=[CH:6][N:5]=2)[CH2:3][CH2:2]1.Br[C:20]1[S:24][C:23]([C:25]2([C:31]3[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=3)[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[N:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.O.CCOC(C)=O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].Cl[Pd]Cl>[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([C:20]3[S:24][C:23]([C:25]4([C:31]5[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=5)[CH2:30][CH2:29][O:28][CH2:27][CH2:26]4)=[N:22][CH:21]=3)=[CH:8][CH:9]=2)[CH2:2][CH2:3]1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 457864292-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 66619354methyl 4-(4-(5-bromothiazol-2-yl)-tetrahydro-2H-pyran-4-yl)benzoate

Product 1

HCID 66619234methyl 4-(4-(5-(6-cyclopropylpyridin-3-yl)thiazol-2-yl)-tetrahydro-2H-pyran-4-yl)benzoate

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8857Ethyl AcetateSolventHCID 86587398Ethanol toluene waterSolvent

Procedure

A mixture of 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (490 mg, 2.00 mmol), methyl 4-(4-(5-bromothiazol-2-yl)-tetrahydro-2H-pyran-4-yl)benzoate (382 mg, 1.00 mmol), potassium carbonate (276 mg, 2.0 mmol), and 1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (PdCl2(dppf), 146 mg, 0.20 mmol) in toluene/ethanol/water (2 mL/1 mL/1 mL) was heated in microwave (Emry's Optimizer) at 110 C for 20 minutes. The reaction mixture was cooled to room temperature and then diluted with EtOAc and filtered. The filtrate was concentrated and purified by Flash Chromatography (SiO2, 95% EtOAC: 5% MeOH) to give methyl 4-(4-(5-(6-cyclopropylpyridin-3-yl)thiazol-2-yl)-tetrahydro-2H-pyran-4-yl)benzoate. MS found for C24H24N2O3S as (M+H)+ 421.42. To the above ester in MeOH/THF/dioxane (1:1:1) (9 mL) was added 3N NaOH (5.0 mL) and stirred at 55° C. After 14 hours, the reaction mixture was concentrated, diluted with water, and neutralized with 6N HCl. The formed solids were filtered and washed with water and dried. MS found for C23H22N2O3S as (M+H)+ 407.04. The acid was used further without purification.

Workup

  1. temperaturewas heated in microwave (Emry's Optimizer) at 110 C for 20 minutes
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. custompurified by Flash Chromatography (SiO2, 95% EtOAC: 5% MeOH)

Sources & evidence

ORD record
ord-e0bc5ca4b2f04943830879b1275f5403
Source dataset
uspto-grants-2012_01
Patent number
US08088771B2

Reaction notes

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