Ethanol → (R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acid

HRID 1627142Notes

Reaction equation

HRID 1627142 reaction equation
[Cl:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:20]([CH3:22])[CH3:21])[C:13]([O:15]C(C)(C)C)=[O:14])[C:8](=[O:23])[C:7]3=[CH:24][N:25](S(C4C=CC(C)=CC=4)(=O)=O)[C:5]([C:6]=23)=[N:4][CH:3]=1.CCO.[OH-].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[C:11]2[CH2:10][N:9]([C@H:12]([CH:20]([CH3:21])[CH3:22])[C:13]([OH:15])=[O:14])[C:8](=[O:23])[C:7]3=[CH:24][NH:25][C:5]([C:6]=23)=[N:4][CH:3]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 58293533(R)-tert-butyl 2-(6-chloro-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoate

Product 1

HCID 67224695(R)-2-(6-chloro-3-oxopyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoic acidYield 110.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of (R)-tert-butyl 2-(6-chloro-3-oxo-1-tosylpyrrolo[4,3,2-de][2,6]naphthyridin-4(1H,3H,5H)-yl)-3-methylbutanoate (650 mg, 1.25 mmol), EtOH (4 mL), and aqueous NaOH (1N, 2 mL) was stirred at room temperature for 40 min. The mixture was subsequently diluted with DCM and washed with brine. The organics were dried over MgSO4 and concentrated in vacuo. Purification by silica gel chromatography (5% MeOH/DCM) gave a yellow oil (425 mg), which was dissolved in 50% TFA/DCM. The solution was stirred at room temperature for 1 h, concentrated, and dried under vacuum to give the title compound as a yellow solid (360 mg, 93%). 1H NMR (500 MHz, CD3OD) δ 0.91 (d, J=7.0 Hz, 3H), 1.11 (d, J=7.0 Hz, 3H), 2.36-2.47 (m, 1H), 4.80-5.08 (m, 3H), 7.76 (s, 1H), 8.19 (s, 1H). [M+H] calc'd for C14H14ClN3O3, 308, 310; found, 308, 310.

Workup

  1. washwashed with brine
  2. dry with materialThe organics were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customPurification by silica gel chromatography (5% MeOH/DCM)

Sources & evidence

ORD record
ord-5c8136ff6db740d88a2647eb1e33cb18
Source dataset
uspto-grants-2014_07
Patent number
US08785429B2

Reaction notes

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