Tetrahydrofuran → HCID 89720588, compound

HRID 623991Notes

Reaction equation

HRID 623991 reaction equation
[CH2:1]1[CH2:5]O[CH2:3][CH2:2]1.[OH:6][C:7]12[CH2:16][CH:11]3[CH2:12][CH:13]([CH2:15][CH:9]([N:10]3[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:8]1)[CH2:14]2.[H-].[K+].C1(CBr)CC1>CCOC(C)=O>[CH:1]1([CH2:5][O:6][C:7]23[CH2:8][CH:9]4[CH2:15][CH:13]([CH2:12][CH:11]([N:10]4[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:16]2)[CH2:14]3)[CH2:3][CH2:2]1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 81503BromomethylcyclopropaneHCID 82127Potassium hydrideHCID 89714735HCID 89714735, compound

Product 1

HCID 89720588HCID 89720588, compoundYield 80%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A 15 mL seal tube fitted with magnetic stirrer was charged with 5 mL of THF, tert-butyl 5-hydroxy-2-azatricyclo[3.3.1.13,7]decane-2-carboxylate, Intermediate-6 (50 mg, 0.2 mmol). To the tube, potassium hydride (20 mg, 0.5 mmol) was added at 0° C., under N2 atm. The reaction mass was stirred at room temperature for 30 minutes. To this mixture, cyclopropyl methyl bromide (40 mg, 0.3 mmol) was slowly added at 0° C. and the resulting reaction mass was refluxed at 60° C. under sealed condition for 12 hrs. After completion of the reaction (reaction was monitored by TLC), reaction mixture was quenched with cold water and extracted with ethyl acetate (25 ml×3). The organic layer was washed with sodium chloride solution, dried over anhydrous sodium sulfate and concentrated to give crude Intermediate-17, which was subjected to column chromatogram (18% EtOAc in PE) to obtain an oily mass (50 mg, yield=80%).

Workup

  1. customA 15 mL seal tube
  2. customfitted with magnetic stirrer
  3. customthe resulting reaction mass
  4. temperaturewas refluxed at 60° C.
  5. customunder sealed condition for 12 hrs
  6. customAfter completion of the reaction (reaction was monitored by TLC), reaction mixture
  7. customwas quenched with cold water
  8. extractionextracted with ethyl acetate (25 ml×3)
  9. washThe organic layer was washed with sodium chloride solution
  10. dry with materialdried over anhydrous sodium sulfate
  11. concentrationconcentrated
  12. customto give crude Intermediate-17, which
  13. customto obtain an oily mass (50 mg, yield=80%)

Sources & evidence

ORD record
ord-d74d6eede9f946618d48b6acd53f7397
Source dataset
uspto-grants-2016_04
Patent number
US09303016B2

Reaction notes

Loading…