Lithium Hexamethyldisilazide → 1-(4-(4-Bromo-3,5-dimethoxyphenyl)thiazol-2-yl)-2-methoxy-2-(4-morpholinophenyl)ethanone

HRID 2359151Notes

Reaction equation

HRID 2359151 reaction equation
[Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2[N:11]=[CH:12][S:13][CH:14]=2)=[CH:4][C:3]=1[O:15][CH3:16].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.CON(C)[C:30](=[O:46])[CH:31]([O:44][CH3:45])[C:32]1[CH:37]=[CH:36][C:35]([N:38]2[CH2:43][CH2:42][O:41][CH2:40][CH2:39]2)=[CH:34][CH:33]=1>C1COCC1>[Br:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][C:5]([C:10]2[N:11]=[C:12]([C:30](=[O:46])[CH:31]([O:44][CH3:45])[C:32]3[CH:33]=[CH:34][C:35]([N:38]4[CH2:39][CH2:40][O:41][CH2:42][CH2:43]4)=[CH:36][CH:37]=3)[S:13][CH:14]=2)=[CH:4][C:3]=1[O:15][CH3:16]

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 58431993N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl)acetamideHCID 584320464-(4-Bromo-3,5-dimethoxyphenyl)thiazole

Product 1

HCID 584320811-(4-(4-Bromo-3,5-dimethoxyphenyl)thiazol-2-yl)-2-methoxy-2-(4-morpholinophenyl)ethanoneYield 29.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a −78° C. solution of 4-(4-bromo-3,5-dimethoxyphenyl)thiazole (0.096 g, 0.32 mmol) in anhydrous THF (2 mL) under argon was added a solution of LiHMDS (1.0 M in THF, 0.35 mmol) dropwise. After stirring for 30 min, a solution of N,2-dimethoxy-N-methyl-2-(4-morpholinophenyl)acetamide (0.121 g, 0.41 mmol) in anhydrous THF (1.5 mL, 1.0 mL) was added dropwise. After stirring for 35 min, the cold bath was removed and the reaction was allowed to warm to room temp. The mixture was quenched with brine and diluted with EtOAc. The layers were separated and the organic layer was washed with brine, dried over Na2SO4 and concentrated. Purification by chromatography (25-45% EtOAc-hexanes) gave 1-(4-(4-bromo-3,5-dimethoxyphenyl)thiazol-2-yl)-2-methoxy-2-(4-morpholinophenyl)ethanone as a yellow solid (0.050 g, 29% yield). MS: m/z 533.1 [M+H]+.

Workup

  1. stirringAfter stirring for 35 min
  2. customthe cold bath was removed
  3. customThe mixture was quenched with brine
  4. additiondiluted with EtOAc
  5. customThe layers were separated
  6. washthe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customPurification by chromatography (25-45% EtOAc-hexanes)

Sources & evidence

ORD record
ord-4bf46b917737489cba8ae84a4287ff98
Source dataset
uspto-grants-2014_04
Patent number
US08685975B2

Reaction notes

Loading…