Sulfuric Acid → methyl 2-hydroxy-2-(6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

HRID 1473237Notes

Reaction equation

HRID 1473237 reaction equation
[OH:1][CH:2]([C:7]1[N:12]([CH3:13])[C:11](=[O:14])[C:10]2[N:15](CC3C=CC(OC)=CC=3)[CH:16]=[CH:17][C:9]=2[C:8]=1[C:27]1[C:28]([CH3:37])=[C:29]2[C:34](=[CH:35][CH:36]=1)[O:33][CH2:32][CH2:31][CH2:30]2)[C:3]([O:5][CH3:6])=[O:4].OS(O)(=O)=O.C1(OC)C=CC=CC=1.CO.C(Cl)Cl>FC(F)(F)C(O)=O>[OH:1][CH:2]([C:7]1[N:12]([CH3:13])[C:11](=[O:14])[C:10]2[NH:15][CH:16]=[CH:17][C:9]=2[C:8]=1[C:27]1[C:28]([CH3:37])=[C:29]2[C:34](=[CH:35][CH:36]=1)[O:33][CH2:32][CH2:31][CH2:30]2)[C:3]([O:5][CH3:6])=[O:4]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 7519AnisoleHCID 21226129Dichloromethane methanolHCID 89463114methyl 2-hydroxy-2-(1-(4-methoxybenzyl)-6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

Product 1

HCID 89462801methyl 2-hydroxy-2-(6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetateYield 62.9%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

An ice cold solution of methyl 2-hydroxy-2-(1-(4-methoxybenzyl)-6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (880 mg, 1.751 mmol) in Trifluoroacetic acid (TFA) (3.5 mL) was treated with conc. H2SO4 (0.262 mL, 4.92 mmol) and anisole (0.525 mL, 4.81 mmol). After stirring for 1 hour, the reaction was warmed to rt for 2 hours, and then quenched with sat. NaHCO3 until neutral. The mixture was extracted with EtOAc, washed with Brine, dried with Na2SO4, filtered, and concentrated. Purification with column chromatography (0-100% EtOAc/Hexane, then 0-20% MeOH/DCM) afforded methyl 2-hydroxy-2-(6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (421.4 mg, 1.102 mmol, 62.9% yield) as yellow oil: LCMS (m/z) ES+=383 (M+1).

Workup

  1. customquenched with sat. NaHCO3 until neutral
  2. extractionThe mixture was extracted with EtOAc
  3. washwashed with Brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification with column chromatography (0-100% EtOAc/Hexane

Sources & evidence

ORD record
ord-c6c77d499361491790e80ed000245c5d
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

Loading…