1-Bromo-2-methylpropane → HCID 178490655, compound

HRID 1028177Notes

Reaction equation

HRID 1028177 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:22][CH3:23])=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[S:11][C:12]2[C:18]([CH3:20])([CH3:19])[O:17][CH2:16][CH2:15][C:13]=2[N:14]=1)=[O:8].[CH3:24][C:25]([CH3:28])([O-])[CH3:26].[K+].BrCC(C)C>CN(C)C=O.O1CCCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:22][CH3:23])=[C:6]([CH:21]=1)[C:7](/[N:9]=[C:10]1\[S:11][C:12]2[C:18]([CH3:19])([CH3:20])[O:17][CH2:16][CH2:15][C:13]=2[N:14]\1[CH2:24][CH:25]([CH3:28])[CH3:26])=[O:8]

Participants

6

Reactant 3

HCID 65551-Bromo-2-methylpropaneHCID 23665647Potassium tert-butoxideHCID 871795845-Chloro-n-(4,4-dimethyl-6,7-dihydro-4h-pyrano[4,3-d]thiazol-2-yl)-2-methoxybenzamide

Product 1

HCID 178490655HCID 178490655, compoundYield 29%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of Example 3F (1.0 g, 2.8 mmol) in N,N-dimethylformamide/tetrahydrofuran (1:4, 20 mL) was added potassium tert-butoxide (0.35 g, 3.1 mmol, Aldrich), 1-bromo-2-methylpropane (0.43 g, 3.1 mmol, Aldrich) and tetrabutyl ammonium iodide (0.1 g, 0.3 mmol, Aldrich). After stirring at 80° C. for 16 h, the reaction mixture was cooled to room temperature and quenched with saturated aqueous NaHCO3 (20 mL). The aqueous layer was extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography using an Analogix® Intelliflash280 ™ (SiO2, 0-100% ethyl acetate in hexanes) to afford 90 mg (29%) of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.81-0.88 (m, 3H), 0.91 (s, 3H), 1.46 (s, 6H), 2.29 (t, 1H), 2.67 (t, J=5.4 Hz, 2H), 3.79 (s, 3H), 3.88-4.11 (m, 4H), 7.12 (d, J=9.1 Hz, 1H), 7.46 (dd, J=8.7, 2.8 Hz, 1H), 7.67 (d, J=3.2 Hz, 1H); MS (ESI+) m/z 409 (M+H)+; Anal. Calculated CO1H25ClN3O3S: C, 58.74; H, 60.16; N, 6.85. Found: C, 58.80; H, 5.97; N, 6.88.

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. customquenched with saturated aqueous NaHCO3 (20 mL)
  3. extractionThe aqueous layer was extracted with ethyl acetate (3×20 mL)
  4. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-768eb43b81c849258e415b2cc13a84b4
Source dataset
uspto-grants-2014_05
Patent number
US08735434B2

Reaction notes

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