Methyl iodide → (4S,5S)-Tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-4-((2-chloro-6-methylpyridin-4-yl)methyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 1697248Notes

Reaction equation

HRID 1697248 reaction equation
[CH3:1]N(C)CCO.[Li+].CCC[CH2-].[Si:12]([O:19][CH2:20][C@H:21]1[O:25][C:24]([CH3:27])([CH3:26])[N:23]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[C@H:22]1[CH2:35][C:36]1[CH:41]=[CH:40][N:39]=[C:38]([Cl:42])[CH:37]=1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].CI>C1COCC1>[Si:12]([O:19][CH2:20][C@H:21]1[O:25][C:24]([CH3:27])([CH3:26])[N:23]([C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])[C@H:22]1[CH2:35][C:36]1[CH:41]=[C:40]([CH3:1])[N:39]=[C:38]([Cl:42])[CH:37]=1)([C:15]([CH3:16])([CH3:17])[CH3:18])([CH3:13])[CH3:14]

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 79022-(Dimethylamino)ethanolHCID 61028n-Butyl lithiumHCID 86635710(4S,5S)-Tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-4-((2-chloropyridin-4-yl)methyl)-2,2-dimethyloxazolidine-3-carboxylate

Product 1

HCID 86614126(4S,5S)-Tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-4-((2-chloro-6-methylpyridin-4-yl)methyl)-2,2-dimethyloxazolidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Dimethylethanolamine (0.128 ml, 1.27 mmol) was added to anhydrous hexanes (1.4 L) and cooled to 0° C. N-BUTYLLITHIUM (2.5 M in hexanes)(1.02 ml, 2.55 mmol) was added dropwise and stirred for 30 minutes before being cooled to −78° C. (4S,5S)-Tert-butyl 5-((tert-butyldimethylsilyloxy)methyl)-4-((2-chloropyridin-4-yl)methyl)-2,2-dimethyloxazolidine-3-carboxylate (0.200 g, 0.425 mmol) in hexanes (1 mL) was added dropwise and the solution was stirred for 1 hour at −78° C. to give a dark orange solution. MeI (0.106 ml, 1.70 mmol) in THF (3.2 mL) was added dropwise and the reaction was allowed to slowly warm to 0° C. and was quenched with saturated aqueous ammonium chloride. The reaction was diluted with ethyl acetate and water and separated. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with water, brine, dried over sodium sulfate, and concentrated to give the titled compound which was used directly for the next step without purification.

Workup

  1. additionwas added dropwise
  2. stirringthe solution was stirred for 1 hour at −78° C.
  3. customto give a dark orange solution
  4. temperatureto slowly warm to 0° C.
  5. customwas quenched with saturated aqueous ammonium chloride
  6. additionThe reaction was diluted with ethyl acetate and water
  7. customseparated
  8. extractionThe aqueous layer was extracted with ethyl acetate
  9. washthe combined organic layers were washed with water, brine
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-64362959ed9c45c999fe116bd75a767e
Source dataset
uspto-grants-2012_04
Patent number
US08163909B2

Reaction notes

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