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

HRID 1473218Notes

Reaction equation

HRID 1473218 reaction equation
[CH3:1][N:2]1[C:6]2[C:7](=[O:25])[N:8]([CH3:24])[C:9]([CH:18]([OH:23])[C:19]([O:21][CH3:22])=[O:20])=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)[C:5]=2[CH:4]=[CH:3]1.C(O[C:30]([CH3:33])([CH3:32])[CH3:31])(=O)C.Cl(O)(=O)(=O)=O>>[C:30]([O:23][CH:18]([C:9]1[N:8]([CH3:24])[C:7](=[O:25])[C:6]2[N:2]([CH3:1])[CH:3]=[CH:4][C:5]=2[C:10]=1[C:11]1[CH:12]=[CH:13][C:14]([CH3:17])=[CH:15][CH:16]=1)[C:19]([O:21][CH3:22])=[O:20])([CH3:33])([CH3:32])[CH3:31]

Participants

4

Reactant 3

HCID 10908tert-Butyl acetateHCID 24247Perchloric AcidHCID 89463238methyl 2-(1,6-dimethyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-hydroxyacetate

Product 1

HCID 89463043methyl 2-(tert-butoxy)-2-(1,6-dimethyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetateYield 73.2%

Procedure

An ice cold solution of methyl 2-(1,6-dimethyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)-2-hydroxyacetate (28 mg, 0.082 mmol) in tert-butyl acetate (1111 μl, 8.23 mmol) was treated with perchloric acid (7.07 μl, 0.082 mmol), and stirred for 20 min. The reaction was then kept in the refrigerator without stirring for 2 days. 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) gave methyl 2-(tert-butoxy)-2-(1,6-dimethyl-7-oxo-4-(p-tolyl)-6,7-dihydro-1H-pyrrolo[2,3-c]pyridin-5-yl)acetate (23.6 mg, 0.060 mmol, 72.4% yield). The intermediate was dissolved in Methanol (500 μl) and Tetrahydrofuran (THF) (500 μl), treated with 2M LiOH (174 μl, 0.348 mmol), and stirred at 60° C. for 4 hours. The mixture was concentrated and purified with reverse phase chromatography (20-100% MeCN/H2O-0.1% TFA, 12 min) to give title compound (19.6 mg, 0.051 mmol, 87% yield) as white solid: 1H NMR (400 MHz, CHLOROFORM-d) ppm 0.99 (s, 9H), 2.43 (s, 3H), 3.66 (s, 3H), 4.20 (s, 3H), 5.45 (s, 1H), 5.98 (d, J=2.7 Hz, 1H), 6.96 (d, J=2.7 Hz, 1H), 7.24-7.31 (m, 2H), 7.31-7.38 (m, 1H), 7.49-7.57 (m, 1H); LCMS (m/z) ES+=383 (M+1).

Workup

  1. stirringwithout stirring for 2 days
  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-4b70b3bc5cdf427993ef1400e95c3e8e
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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