Isopropanol → Ethyl 2-(7-((3-chlorobenzyl)oxy)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl)acetate

HRID 1748399Notes

Reaction equation

HRID 1748399 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][CH:33]=1)[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH2:11][CH:12]([CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:13](=[O:24])[N:14]2C(OC(C)(C)C)=O)=[CH:9][CH:8]=1.Cl.O1CCOCC1.CC(O)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][CH:33]=1)[CH2:5][O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH2:11][CH:12]([CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])[C:13](=[O:24])[NH:14]2)=[CH:9][CH:8]=1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 204431481,4-Dioxane hydrochlorideHCID 90417137HCID 90417137, compound

Product 1

HCID 90416764Ethyl 2-(7-((3-chlorobenzyl)oxy)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To crude tert-butyl 7-((3-chlorobenzyl)oxy)-3-(2-ethoxy-2-oxoethyl)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate (115.7 g, 244.1 mmol) was added a 4.0 M 1,4-dioxane hydrochloride solution (200 mL, 0.8 mol) in an ice bath. After addition, the ice bath was removed and the reaction was warmed to ambient temperature. The reaction was concentrated to a yellow oil and azeotroped with toluene (2×250 mL) to furnish a brown oil. The oil was diluted in toluene (400 mL) followed by 2-propanol (400 mL). The resulting white ppt that was formed was filtered and washed with 2-propanol to furnish the desired product as a white solid. The mother liquor was concentrated to a brown solid that was triturated with 2-propanol (400 mL), filtered and washed with 2-propanol to furnish a second crop of product (38.3 g). The two crops were combined to give (50.3 g, 55%) of the title compound. 1H NMR (400 MHz, CDCl3) δ 7.88 (s, 1H), 7.43 (s, 1H), 7.35-7.29 (m, 3H), 7.06 (d, J=8.3 Hz, 1H), 6.59 (dd, J=8.3, 2.4 Hz, 1H), 6.39 (d, J=2.4 Hz, 1H), 5.02 (s, 2H), 4.23-4.15 (m, 2H), 3.12-2.92 (m, 3H), 2.92-2.77 (m, 1H), 2.48 (dd, J=16.2, 7.5 Hz, 1H), 1.29 (t, J=7.1 Hz, 3H). [M+H]=374.2.

Workup

  1. additionAfter addition
  2. customthe ice bath was removed
  3. concentrationThe reaction was concentrated to a yellow oil
  4. customazeotroped with toluene (2×250 mL)
  5. customto furnish a brown oil
  6. customThe resulting white ppt that was formed
  7. filtrationwas filtered
  8. washwashed with 2-propanol

Sources & evidence

ORD record
ord-ad3e729cc4854858a86b5fee3557bf59
Source dataset
uspto-grants-2015_10
Patent number
US09150572B2

Reaction notes

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