Lithium diisopropylamide → N-(4-chloro-3-methylisothiazol-5-yl)-2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propionamide

HRID 48154Notes

Reaction equation

HRID 48154 reaction equation
C([N-]C(C)C)(C)C.[Li+].[NH2:9][C:10]1[S:14][N:13]=[C:12]([CH3:15])[C:11]=1[Cl:16].[CH3:17][C:18]([CH3:36])([CH3:35])[CH2:19][C:20]1[O:21][C:22]2[CH:28]=[CH:27][C:26]([CH:29]([CH3:34])[C:30](OC)=[O:31])=[CH:25][C:23]=2[N:24]=1>O1CCCC1>[Cl:16][C:11]1[C:12]([CH3:15])=[N:13][S:14][C:10]=1[NH:9][C:30](=[O:31])[CH:29]([C:26]1[CH:27]=[CH:28][C:22]2[O:21][C:20]([CH2:19][C:18]([CH3:35])([CH3:17])[CH3:36])=[N:24][C:23]=2[CH:25]=1)[CH3:34]

Participants

5

Reactant 3

HCID 2724682Lithium diisopropylamideHCID 112405714-Chloro-3-methyl-1,2-thiazol-5-amineHCID 22742115HCID 22742115, compound

Product 1

HCID 22742107N-(4-chloro-3-methylisothiazol-5-yl)-2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propionamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

Lithium diisopropylamide (2.0 molar solution in tetrahydrofuran/ethylbenzene/heptane, 1.46 ml, 0.0029 mole) was added dropwise to a chilled solution of 5-amino-4-chloro-3-methylisothiazole (0.44 g, 0.0029 mole) [preparation as in Example 1, Step 1] in tetrahydrofuran (20 ml) and the solution was stirred at 0° C. for 1 hour. A solution of methyl 2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propionate (0.80 g, 0.0029 mole) [from previous step] in tetrahydrofuran (5 ml) was added dropwise and once the addition was complete the mixture was stirred at 0° C. for 30 minutes and then at room temperature overnight. The mixture was quenched with water, acidified with aqueous ammonium chloride solution and extracted with ethyl acetate. The organic extract was dried over anhydrous magnesium sulfate, filtered and the filtrate evaporated in vacuo. Further purification by flash column chromatography, eluting with ethyl acetate:hexane at 1:4 by volume gave N-(4-chloro-3-methylisothiazol-5-yl)-2-[2-(2,2-dimethylpropyl)benzoxazol-5-yl]propionamide as a colourless solid.

Workup

  1. additiononce the addition
  2. stirringwas stirred at 0° C. for 30 minutes
  3. customat room temperature
  4. customovernight
  5. customThe mixture was quenched with water
  6. extractionextracted with ethyl acetate
  7. extractionThe organic extract
  8. dry with materialwas dried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. customthe filtrate evaporated in vacuo
  11. customFurther purification by flash column chromatography
  12. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-7efe2b2dce7c4b1bbe8ee3447c08e0da
Source dataset
uspto-grants-2004_03
Patent number
US06703347B2

Reaction notes

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