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

HRID 1473238Notes

Reaction equation

HRID 1473238 reaction equation
[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:18]1[C:19]([CH3:28])=[C:20]2[C:25](=[CH:26][CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:3]([O:5][CH3:6])=[O:4].C(O[C:33]([CH3:36])([CH3:35])[CH3:34])(=O)C.Cl(O)(=O)(=O)=O>CO.C(Cl)Cl>[C:33]([O: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:18]1[C:19]([CH3:28])=[C:20]2[C:25](=[CH:26][CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:3]([O:5][CH3:6])=[O:4])([CH3:36])([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 89462801methyl 2-hydroxy-2-(6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

Product 1

HCID 89462937methyl 2-(tert-butoxy)-2-(6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetateYield 46.1%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

An ice cold solution of 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 (425 mg, 1.111 mmol) in tert-butyl acetate (15.000 mL, 111 mmol) was treated with perchloric acid (0.191 mL, 2.223 mmol), and stirred for 5 min. The reaction was then kept in the refrigerator without stirring overnight. The reaction was quenched with sat. NaHCO3 at 0° C., extracted with EtOAc 2×, washed with Brine, dried with Na2SO4, filtered, and concentrated. Purification with column chromatography (0-100% EtOAc/Hexane, then 0-20% MeOH/DCM) gave methyl 2-(tert-butoxy)-2-(6-methyl-4-(5-methylchroman-6-yl)-7-oxo-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (224.7 mg, 0.512 mmol, 46.1% yield) as off white solid. NMR showed 2:1 diastereomer. 1H NMR (400 MHz, CHLOROFORM-d) ppm 9.93 (br. s., 1H), 7.19-7.12 (m, 1.4H), 6.99 (d, J=8.4 Hz, 0.6H), 6.77-6.68 (m, 1H), 5.91-5.77 (m, 1H), 5.36-5.10 (m, 1H), 4.27-4.16 (m, 2H), 3.81-3.74 (m, 3H), 3.74-3.62 (m, 3H), 2.77-2.60 (m, 2H), 2.17-2.06 (m, 2H), 1.95-1.88 (m, 3H), 1.16-1.07 (m, 6H), 1.00-0.94 (m, 3H); LCMS (m/z) ES+=439 (M+1).

Workup

  1. stirringwithout stirring overnight
  2. customThe reaction was quenched with sat. NaHCO3 at 0° C.
  3. extractionextracted with EtOAc 2×
  4. washwashed with Brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification with column chromatography (0-100% EtOAc/Hexane

Sources & evidence

ORD record
ord-40f9aac247584fb1869063b2cbe5c6cb
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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