Acetonitrile → Methyl 2-tert-Butyl-4-((2-methyl-3-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)phenylamino)methyl)thiazole-5-carboxylate

HRID 872174Notes

Reaction equation

HRID 872174 reaction equation
[CH3:1][C:2]1[C:8]([B:9]2[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]2)=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:25][C:26]1C=[C:29]([C:31]([CH3:34])([CH3:33])[CH3:32])[S:28][C:27]=1[C:35]([O:37][CH3:38])=[O:36].C(#[N:41])C>>[C:31]([C:29]1[S:28][C:27]([C:35]([O:37][CH3:38])=[O:36])=[C:26]([CH2:25][NH:4][C:3]2[CH:5]=[CH:6][CH:7]=[C:8]([B:9]3[O:13][C:12]([CH3:15])([CH3:14])[C:11]([CH3:17])([CH3:16])[O:10]3)[C:2]=2[CH3:1])[N:41]=1)([CH3:34])([CH3:33])[CH3:32]

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 467380052-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 66610052Methyl 3-(bromomethyl)-5-tert-butylthiophene-2-carboxylate

Product 1

HCID 66634683Methyl 2-tert-Butyl-4-((2-methyl-3-(4,4,5,5-tetramethyl-1,3,2dioxaborolan-2-yl)phenylamino)methyl)thiazole-5-carboxylateYield 56%

Conditions

Temperature
0 °C

Procedure

2-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (466.2 mg, 2.0 mmol) and cesium carbonate (782.0 mg, 2.4 mmol) were suspended in anhydrous acetonitrile (20 mL) and the mixture was cooled to 0° C. Methyl 3-(bromomethyl)-5-tert-butylthiophene-2-carboxylate (109c) (584.4 mg, 2.0 mmol) was then added. The resulting mixture was allowed to gradually warm to room temperature, then stirred at 40° C. overnight. The reaction mixture was filtered through Celite®, and the filtrate was concentrated. The residue was purified on silica eluted with a gradient of 0 to 10% Ethyl acetate in heptane to afford methyl 2-tert-butyl-4-((2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylamino)methyl)thiazole-5-carboxylate (109d) (501.6 mg, 56%).

Workup

  1. temperatureto gradually warm to room temperature
  2. filtrationThe reaction mixture was filtered through Celite®
  3. concentrationthe filtrate was concentrated
  4. customThe residue was purified on silica
  5. washeluted with a gradient of 0 to 10% Ethyl acetate in heptane

Sources & evidence

ORD record
ord-888c4559710d4497b6ed4f94d4ca84f9
Source dataset
uspto-grants-2015_03
Patent number
US08975260B2

Reaction notes

Loading…