Methacrolein → HCID 67093115, compound

HRID 1261829Notes

Reaction equation

HRID 1261829 reaction equation
Cl.CO[C:4](=O)[C@H:5]([CH3:7])N.[O:9]=[CH:10][C:11](=[CH2:13])[CH3:12].S([O-])([O-])(=O)=[O:15].[Mg+2].C([BH3-])#N.[Na+].[CH3:24][O:25][C:26](=[O:34])[C@@H:27]([NH:29][CH2:30][C:31]([CH3:33])=C)[CH3:28].[CH3:35][O:36]C(=O)[C@@H](NCC(C)C)C>CO>[CH3:24][O:25][C:26](=[O:34])[C@@H:27]([N:29]([C:35]([O:9][CH2:10][C:11]1[CH:12]=[CH:7][CH:5]=[CH:4][CH:13]=1)=[O:36])[CH2:30][C:31](=[O:15])[CH3:33])[CH3:28]

Participants

8

Reactant 6

HCID 6562MethacroleinHCID 24083Sulfuric acid magnesium salt (1:1)HCID 2733257Alanine methyl ester hydrochlorideHCID 5003444Sodium cyanoborohydrideHCID 43723603HCID 43723603, compoundHCID 86652422HCID 86652422, compound

Product 1

HCID 67093115HCID 67093115, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of L-alanine methyl ester hydrochloride (6.00 g, 43.0 mmol) in MeOH (120 mL) were added at 0° C. methacrolein (4.12 g, 56 mmol), magnesium sulfate (46.6 g, 387 mmol), and sodium cyanoborohydride (3.70 g, 56 mmol). The ice bath was removed, then after 16 h the excess reagent was destroyed by careful addition of sat. aq. sodium hydrogencarbonate solution at 0° C. The reaction mixture was partitioned between sat. aq. sodium hydrogencarbonate solution and EtOAc. The organic layer was washed with brine, dried (MgSO4), filtered, and evaporated to afford a 1:1 mixture of (S)-2-(2-methyl-allylamino)-propionic acid methyl ester and (S)-2-isobutylamino-propionic acid methyl ester title compound (5.4 g). This was reacted with benzyl chloroformate in analogy with intermediate 1B, leading to a mixture of (S)-2-[benzyloxycarbonyl-(2-methyl-allyl)-amino]-propionic acid methyl ester and (S)-2-(benzyloxycarbonyl-isobutyl-amino)-propionic acid methyl ester (9.8 g). This was suspended in acetone (60 mL) and water (60 mL), then sodium periodate (13.8 g, 64 mmol) and osmium tetroxide solution (2.5% in tert-butylalcohol, 2.2 mL, 0.43 mmol) were added at 0° C. The ice bath was removed, then after 16 h the reaction mixture was partitioned between EtOAc and water. The organic layer was dried over magnesium sulfate, filtered, and evaporated. Chromatography (SiO2; heptane-EtOAc gradient) produced the title compound (1.88 g, 14%). Colourless oil, MS: 294.1 (M+H)+.

Workup

  1. customThe ice bath was removed
  2. customafter 16 h the excess reagent was destroyed by careful addition of sat. aq. sodium hydrogencarbonate solution at 0° C
  3. customThe reaction mixture was partitioned between sat. aq. sodium hydrogencarbonate solution and EtOAc
  4. washThe organic layer was washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto afford

Sources & evidence

ORD record
ord-51d648a543c54a1491a7ee847e1b0948
Source dataset
uspto-grants-2013_06
Patent number
US08471004B2

Reaction notes

Loading…