Water → HCID 101175893, compound

HRID 408153Notes

Reaction equation

HRID 408153 reaction equation
[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[CH2:6]([O:8][P:9]([N:14]1[CH:20]2[CH:15]1[CH2:16][CH2:17][N:18]([C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])[CH2:19]2)([O:11][CH2:12][CH3:13])=[O:10])[CH3:7].O>C1COCC1>[CH:1]1([C@@H:15]2[CH2:16][CH2:17][N:18]([C:21]([O:23][CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:22])[CH2:19][C@H:20]2[NH:14][P:9]([O:8][CH2:6][CH3:7])([O:11][CH2:12][CH3:13])=[O:10])[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 962WaterHCID 59455678Benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylateHCID 178418630HCID 178418630, compound

Product 1

HCID 101175893HCID 101175893, compoundYield 59%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a suspension of Cu(I)I (0.15 g, 0.77 mmol) in THF (20 mL) was slowly added 0.50M cyclopropylmagnesium bromide (61.2 mL, 30.6 mmol) in THF at −30° C. After stirring at that temperature for 15 minutes, a solution of benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate (2.82 g, 7.66 mmol; Example H, Step D) in THF (10 mL) was added at −30° C., and then the mixture was slowly warmed to room temperature and stirred at room temperature for 2 hours. Water (50 mL) was added and extracted with ethyl acetate (2×40 mL), washed with brine, dried (sodium sulfate) and concentrated in vacuo. The residue obtained was purified by flash chromatography on silica gel (ethyl acetate) to give trans-benzyl 4-cyclopropyl-3-(diethoxyphosphorylamino)piperidine-1-carboxylate (1.84 g, 59%).

Workup

  1. customat −30° C
  2. stirringstirred at room temperature for 2 hours
  3. extractionextracted with ethyl acetate (2×40 mL)
  4. washwashed with brine
  5. dry with materialdried (sodium sulfate)
  6. concentrationconcentrated in vacuo
  7. customThe residue obtained
  8. customwas purified by flash chromatography on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-d04cdb607a42477d91ef9068e01420fe
Source dataset
uspto-grants-2014_06
Patent number
US08758830B2

Reaction notes

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