Sodium hydride → methyl 2-[(3S)-1-Cbz-3-pyrolidinyl(cyclohexyl)amino]acetate

HRID 1670012Notes

Reaction equation

HRID 1670012 reaction equation
[H-].[Na+].[C:3]([N:13]1[CH2:17][CH2:16][C@H:15]([NH:18][CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:14]1)([O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:4].Br[CH2:26][C:27]([O:29][CH3:30])=[O:28]>C1COCC1>[C:3]([N:13]1[CH2:17][CH2:16][C@H:15]([N:18]([CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[CH2:26][C:27]([O:29][CH3:30])=[O:28])[CH2:14]1)([O:5][CH2:6][C:7]1[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1)=[O:4]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 60984Methyl bromoacetateHCID 67343263HCID 67343263, compound2×

Product 1

HCID 67379348methyl 2-[(3S)-1-Cbz-3-pyrolidinyl(cyclohexyl)amino]acetateYield 90%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

NaH (60% in mineral oil, 52.0 mg, 1.30 mmol) was placed in a round-bottom flask, filled with nitrogen, and then THF (10 mL) was added. A solution of (3S)-1-Cbz-3-(cyclohexylamino)pyrrolidine (302 mg, 1.00 mmol) prepared in Intermediate 2 in THF was added dropwise at 0° C., and the reaction mixture was stirred for 30 min until no further gas evolution occurred, followed by slow addition of methyl bromoacetate. After 4 h, the reaction, mixture was quenched with water and extracted with EtOAc. The extracts were dried over MgSO4 and concentrated in vacuo, and the residue was purified by column chomatography (EtOAc/Hex=1/2) to give the title compound (227 mg, 90.0%).

Workup

  1. additionfilled with nitrogen
  2. additionwas added dropwise at 0° C.
  3. waitAfter 4 h
  4. customthe reaction, mixture
  5. customwas quenched with water
  6. extractionextracted with EtOAc
  7. dry with materialThe extracts were dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customthe residue was purified by column chomatography (EtOAc/Hex=1/2)

Sources & evidence

ORD record
ord-10f4142bf1eb43fcb524c8da4d5962f8
Source dataset
uspto-grants-2011_08
Patent number
US07989634B2

Reaction notes

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