Ammonium Chloride → tert-butyl (3R,5S)-3-(1-hydroxycyclohexyl)-5-[(2-methylpropyl)amino]piperidine-1-carboxylate

HRID 2192840Notes

Reaction equation

HRID 2192840 reaction equation
[CH3:1][CH:2]([CH3:22])[CH2:3][NH:4][C@@H:5]1[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:8][C@H:7]([C:18]([O:20]C)=O)[CH2:6]1.[CH2-:23][CH2:24][CH2:25][CH2:26][CH2-:27].[Mg+2].[Mg+2].[Br-].[Br-].[Cl-].[NH4+]>C1COCC1>[OH:20][C:18]1([C@@H:7]2[CH2:6][C@H:5]([NH:4][CH2:3][CH:2]([CH3:1])[CH3:22])[CH2:10][N:9]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:8]2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 3637391Pentamethylene-1,5-bis(magnesium bromide)HCID 593566071-tert-butyl 3-methyl (3R,5S)-5-[(2-methylpropyl)amino]piperidine-1,3-dicarboxylate

Product 1

HCID 59625268tert-butyl (3R,5S)-3-(1-hydroxycyclohexyl)-5-[(2-methylpropyl)amino]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-tert-Butyl 3-methyl (3R,5S)-5-[(2-methylpropyl)amino]piperidine-1,3-dicarboxylate (3.0 g) was dissolved in THF (30 ml), a solution (15.2 ml) of 3 M pentamethylenebis(magnesium bromide) in THF was added dropwise under ice-cooling, and the mixture was stirred at room temperature for 3 hr. 2 N Aqueous ammonium chloride solution (50 ml) was added to the reaction solution under ice-cooling, and the mixture was extracted with ethyl acetate, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was subjected to basic silica gel column chromatography, and the fraction eluted with ethyl acetate-hexane (0:10→10:0) was concentrated under reduced pressure to give the object compound (1.3 mg).

Workup

  1. temperaturecooling
  2. temperaturecooling
  3. extractionthe mixture was extracted with ethyl acetate
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. washthe fraction eluted with ethyl acetate-hexane (0:10→10:0)
  7. concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record
ord-2a090ec2e8a748bd9e823450418f2231
Source dataset
uspto-grants-2012_12
Patent number
US08329691B2

Reaction notes

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