Oxalyl chloride → 6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-methyl-3-(1,3-thiazol-2-yl)-1,2-benzoxazole-5-carbaldehyde

HRID 245503Notes

Reaction equation

HRID 245503 reaction equation
C(Cl)(=O)C(Cl)=O.[CH3:7][C@H:8]1[O:13][C@@H:12]([CH3:14])[CH2:11][N:10]([C:15]2[C:28]([C:29](O)=[O:30])=[CH:27][C:18]3[C:19]([C:22]4[S:23][CH:24]=[CH:25][N:26]=4)=[N:20][O:21][C:17]=3[C:16]=2[CH3:32])[CH2:9]1.[H-].C(O[Al](OC(C)(C)C)OC(C)(C)C)(C)(C)C.[Li+]>CN(C=O)C.ClCCl>[CH3:7][C@H:8]1[O:13][C@@H:12]([CH3:14])[CH2:11][N:10]([C:15]2[C:28]([CH:29]=[O:30])=[CH:27][C:18]3[C:19]([C:22]4[S:23][CH:24]=[CH:25][N:26]=4)=[N:20][O:21][C:17]=3[C:16]=2[CH3:32])[CH2:9]1

Participants

6

Reactant 3

HCID 65578Oxalyl chlorideHCID 16710494Lithium tri-tert-butoxyaluminohydrideHCID 673582146-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-methyl-3-(1,3-thiazol-2-yl)-1,2-benzoxazole-5-carboxylic acid2×

Product 1

HCID 866581096-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-methyl-3-(1,3-thiazol-2-yl)-1,2-benzoxazole-5-carbaldehyde

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (0.31 g, 2.4 mmol) was added to a stirred solution of 6-[(2R,6S)-2,6-dimethylmorpholin-4-yl]-7-methyl-3-(1,3-thiazol-2-yl)-1,2-benzoxazole-5-carboxylic acid (Intermediate 326, 0.18 g, 0.4 mmol) and two drops DMF in dichloromethane (5 mL) at 0° C. and the mixture was stirred at room temperature for 2 hours. Solvent was removed under reduced pressure and the residue was dissolved in THF (10 mL) and the solution was cooled to −78° C. and 1M solution of lithium tri(t-butoxy)aluminum hydride (0.28 g, 1.1 mmol) was added slowly and it was stirred for 30 mins at the same temperature. The reaction was quenched with 1.5N hydrochloric acid and extracted with ethyl acetate, the combined organic layers were dried over sodium sulfate and the solvent was removed. The brown viscous oil thus obtained was purified by silica gel column chromatography (20% ethyl acetate in hexane) affording the product as yellow solid. Yield: 0.06 g (35%).

Workup

  1. customSolvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in THF (10 mL)
  3. temperaturethe solution was cooled to −78° C.
  4. stirringit was stirred for 30 mins at the same temperature
  5. customThe reaction was quenched with 1.5N hydrochloric acid
  6. extractionextracted with ethyl acetate
  7. dry with materialthe combined organic layers were dried over sodium sulfate
  8. customthe solvent was removed
  9. customThe brown viscous oil thus obtained
  10. customwas purified by silica gel column chromatography (20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-e76c0023c6344a9fa73cd60e58539b19
Source dataset
uspto-grants-2014_02
Patent number
US08658641B2

Reaction notes

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