Water → tert-Butyl 4-(1-hydroxypropan-2-yl)pyridin-2-ylcarbamate

HRID 2069059Notes

Reaction equation

HRID 2069059 reaction equation
CC(C[AlH]CC(C)C)C.[C:10]([O:14][C:15]([NH:17][C:18]1[CH:23]=[C:22]([CH:24]([CH3:30])[C:25](OCC)=[O:26])[CH:21]=[CH:20][N:19]=1)=[O:16])([CH3:13])([CH3:12])[CH3:11].O.[O-]S([O-])(=O)=O.[Mg+2]>C1COCC1.C(Cl)Cl>[OH:26][CH2:25][CH:24]([C:22]1[CH:21]=[CH:20][N:19]=[C:18]([NH:17][C:15](=[O:16])[O:14][C:10]([CH3:13])([CH3:12])[CH3:11])[CH:23]=1)[CH3:30]

Participants

7

Reactant 4

HCID 962WaterHCID 14487Diisobutylaluminum hydride2×HCID 24083Sulfuric acid magnesium salt (1:1)HCID 58532575Ethyl 2-(2-(tert-butoxycarbonylamino)pyridin-4-yl)propanoate

Product 1

HCID 58532581tert-Butyl 4-(1-hydroxypropan-2-yl)pyridin-2-ylcarbamateYield 53.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of DIBAL (1M in DCM, 13.8 mL, 13.8 mmol) was added dropwise over 10 min to a stirred solution of the ester (52) (1.35 g, 4.59 mmol) in THF (25 mL) under nitrogen at −78° C. The reaction mixture was warmed to RT and then re-cooled to −78° C. and a second aliquot of DIBAL (1M in DCM, 4.5 mL, 4.5 mmol) was added. The reaction mixture was allowed to warm to RT, then cooled to 0° C. and water (5 mL) and then MgSO4 were added. The mixture was diluted with DCM and filtered to remove the solids. The filter cake was washed with EtOAc, MeOH and DCM and the combined filtrate and washings were evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 40 g, 25-50% EtOAc in isohexane, gradient elution) to afford the title compound (53) (0.62 g, 50%): m/z 253 (M+H)+ (ES+).

Workup

  1. temperaturere-cooled to −78° C.
  2. temperatureto warm to RT
  3. temperaturecooled to 0° C.
  4. filtrationfiltered
  5. customto remove the solids
  6. washThe filter cake was washed with EtOAc, MeOH and DCM
  7. customthe combined filtrate and washings were evaporated in vacuo
  8. customThe residue was purified by flash column chromatography (SiO2, 40 g, 25-50% EtOAc in isohexane, gradient elution)

Sources & evidence

ORD record
ord-7249bd5261d441cb895714ab6704fdff
Source dataset
uspto-grants-2012_10
Patent number
US08299073B2

Reaction notes

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