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

HRID 1473213Notes

Reaction equation

HRID 1473213 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[CH:23]=[CH:22][C:21]([CH3:24])=[CH:20][CH:19]=1)[C:3]([O:5][CH3:6])=[O:4].C(O[C:29]([CH3:32])([CH3:31])[CH3:30])(=O)C.Cl(O)(=O)(=O)=O>>[C:29]([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[CH:19]=[CH:20][C:21]([CH3:24])=[CH:22][CH:23]=1)[C:3]([O:5][CH3:6])=[O:4])([CH3:32])([CH3:31])[CH3:30]

Participants

4

Reactant 3

HCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 89473317methyl 2-hydroxy-2-(6-methyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate

Product 1

HCID 89462627methyl 2-(tert-butoxy)-2-(6-methyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetateYield 64.9%

Procedure

An ice cold solution of methyl 2-hydroxy-2-(6-methyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (142 mg, 0.435 mmol) in tert-butyl acetate (2.94 mL, 21.76 mmol) was treated with perchloric acid (0.075 mL, 0.870 mmol), and then kept in the refrigerator without stirring for 2 days. The reaction was quenched with sat. NaHCO3 at 0° C., extracted with EtOAc, washed with Brine, dried with Na2SO4, filtered, and concentrated. Purification with column chromatography (0-100% EtOAc/Hexane) gave methyl 2-(tert-butoxy)-2-(6-methyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (108 mg, 0.282 mmol, 64.9% yield) as off white solid. 1H NMR (400 MHz, CHLOROFORM-d) ppm 9.71 (br. s., 1H), 7.39-7.31 (m, 2H), 7.30-7.24 (m, 2H), 7.18 (t, 1H), 6.09 (t, J=2.5 Hz, 1H), 5.38 (s, 1H), 3.81 (s, 3H), 3.71 (s, 3H), 2.44 (s, 3H), 0.94 (s, 9H); LCMS (m/z) ES+=383 (M+1).

Workup

  1. customThe reaction was quenched with sat. NaHCO3 at 0° C.
  2. extractionextracted 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-f6dc3a7becd94b6f846e1948bd2edfb8
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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