Water → tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-1-methyl-2-oxoethyl]carbamate

HRID 56023Notes

Reaction equation

HRID 56023 reaction equation
Br[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([Cl:9])=[CH:4][N:3]=1.CON(C)[C:13](=[O:24])[C@@H:14]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH3:15].[Cl-].[NH4+].O>O1CCCC1>[Cl:8][C:7]1[C:2]([C:13](=[O:24])[C@@H:14]([NH:16][C:17](=[O:18])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH3:15])=[N:3][CH:4]=[C:5]([Cl:9])[CH:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 25517Ammonium ChlorideHCID 8170902-Bromo-3,5-dichloropyridineHCID 11806530(S)-tert-Butyl (1-(methoxy(methyl)amino)-1-oxopropan-2-yl)carbamate

Product 1

HCID 131736894tert-butyl (S)-N-[2-(3,5-dichloropyridin-2-yl)-1-methyl-2-oxoethyl]carbamateYield 65.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-20 °C

Procedure

To 11.0 g of 2-bromo-3,5-dichloropyridine in 5 ml of tetrahydrofuran, 36.4 ml of a 1.3 M tetrahydrofuran solution of isopropylmagnesium chloride-lithium chloride complex was added dropwise with stirring at −20° C., and after the addition, the mixture was stirred at the same temperature for 15 minutes. Then, to the reaction mixture, 5.0 g of (S)—N-methoxy-N-methyl-2-(tert-butoxycarbonylamino)propionamide in 36 ml of tetrahydrofuran was added dropwise, and after the addition, the mixture was stirred at the same temperature for another 2 hours. After completion of the reaction, the reaction mixture was mixed with 30 ml of saturated aqueous ammonium chloride and 10 ml of water and extracted with ethyl acetate (40 ml×2), the resulting organic layers were combined, washed with water (40 ml×1) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 10:0 to 3:7) to obtain 4.5 g of the desired product as a pale yellow oil.

Workup

  1. additionafter the addition
  2. stirringthe mixture was stirred at the same temperature for 15 minutes
  3. additionafter the addition
  4. stirringthe mixture was stirred at the same temperature for another 2 hours
  5. customAfter completion of the reaction
  6. extractionextracted with ethyl acetate (40 ml×2)
  7. washwashed with water (40 ml×1)
  8. dry with materialdried over saturated aqueous sodium chloride
  9. customanhydrous sodium sulfate, and the solvent was evaporated under reduced pressure
  10. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ef0ec18fbe2c4254804d730e78112b85
Source dataset
uspto-grants-2016_09
Patent number
US09434684B2

Reaction notes

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