3,3-Dimethylbutanal → 5-tert-Butoxycarbonylaminomethyl-2-(1-hydroxy-3,3-dimethyl-butyl)-pyridine

HRID 911616Notes

Reaction equation

HRID 911616 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][NH:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])=[CH:9][N:8]=1.[CH3:22][C:23]([CH3:28])([CH3:27])[CH2:24][CH:25]=[O:26]>C1COCC1>[C:18]([O:17][C:15]([NH:14][CH2:13][C:10]1[CH:11]=[CH:12][C:7]([CH:25]([OH:26])[CH2:24][C:23]([CH3:28])([CH3:27])[CH3:22])=[N:8][CH:9]=1)=[O:16])([CH3:21])([CH3:20])[CH3:19]

Participants

5

Reactant 3

HCID 763353,3-DimethylbutanalHCID 49761677tert-Butyl ((6-bromopyridin-3-yl)methyl)carbamateHCID 178418339Butyllithium

Product 1

HCID 576559825-tert-Butoxycarbonylaminomethyl-2-(1-hydroxy-3,3-dimethyl-butyl)-pyridineYield 55%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add slowly butyllithium (1.088 mL, 1.741 mmol, 1.6M solution in hexane) to a solution of 2-bromo-5-tert-butoxycarbonylaminomethyl-pyridine (200 mg, 0.696 mmol) in anhydrous THF (10 mL) at −78° C. Stir the mixture at this temperature for 35 min. Add 3,3-dimethylbutyraldehyde (0.219 mL, 1.741 mmol) and stir the mixture at −78° C. for 3 h. Quench the reaction mixture at −78° C. with brine. Extract the aqueous phase with EtOAc (3×15 mL). Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Purify The crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (3:2) to afford the desired intermediate as a colorless oil (118 mg, 55%). MS (ES+) m/z: 309 (M+H)+.

Workup

  1. customQuench the reaction mixture at −78° C. with brine
  2. extractionExtract the aqueous phase with EtOAc (3×15 mL)
  3. dry with materialDry the combined organic extracts over Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate in vacuo
  6. customPurify The crude mixture by chromatography on silica gel eluting with hexane and hexane/EtOAc (3:2)

Sources & evidence

ORD record
ord-f88704a246da4dd89456101076230f2e
Source dataset
uspto-grants-2011_09
Patent number
US08022062B2

Reaction notes

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