2-Hydroxyisobutyric acid → 2-methyl-1-[5-(methyloxy)-6-nitro-2,3-dihydro-1H-indol-1-yl]-1-oxo-2-propanol

HRID 1014329Notes

Reaction equation

HRID 1014329 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][C:12]=1[N+:13]([O-:15])=[O:14])[NH:9][CH2:8][CH2:7]2.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH:40][C:41]([CH3:46])([CH3:45])[C:42](O)=[O:43].CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:45][C:41]([OH:40])([CH3:46])[C:42]([N:9]1[C:10]2[C:6](=[CH:5][C:4]([O:3][CH3:2])=[C:12]([N+:13]([O-:15])=[O:14])[CH:11]=2)[CH2:7][CH2:8]1)=[O:43]

Participants

6

Reactant 4

HCID 116712-Hydroxyisobutyric acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673167385-(methyloxy)-6-nitro-2,3-dihydro-1H-indole hydrochloride

Product 1

HCID 594421262-methyl-1-[5-(methyloxy)-6-nitro-2,3-dihydro-1H-indol-1-yl]-1-oxo-2-propanolYield 69.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 5-(methyloxy)-6-nitro-2,3-dihydro-1H-indole hydrochloride (1 g, 4.34 mmol) in DMF (50 mL) was added HATU (9.89 g, 26.0 mmol), 2-hydroxy-2-methylpropanoic acid (0.677 g, 6.50 mmol), and DIPEA (2.272 mL, 13.01 mmol). After stirring overnight at rt, the solvent was removed, the residue was redissolved in DCM (100 mL), washed with 1M HCl (100 mL), adsorbed to silica gel, and purified by column chromatography (10% to 40% ethyl acetate/hexanes) to afford 2-methyl-1-[5-(methyloxy)-6-nitro-2,3-dihydro-1H-indol-1-yl]-1-oxo-2-propanol (0.84 g, 69%). ESIMS (M+H)+=281.

Workup

  1. customthe solvent was removed
  2. dissolutionthe residue was redissolved in DCM (100 mL)
  3. washwashed with 1M HCl (100 mL)
  4. custompurified by column chromatography (10% to 40% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-38d3fdc5f32448689d578ca0bfb4894f
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

Loading…