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

HRID 577963Notes

Reaction equation

HRID 577963 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)aluminium 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-0c41d7c247654dfbaa70fd8311eef2fe
Source dataset
uspto-grants-2015_05
Patent number
US09040528B2

Reaction notes

Loading…