Phosphorus oxychloride → HCID 86618849, compound

HRID 1367732Notes

Reaction equation

HRID 1367732 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH:8]([O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[C:13](O)[CH:12]=2)[CH2:7][N:6]1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:4].O=P(Cl)(Cl)[Cl:33]>>[CH3:1][O:2][C:3]([CH:5]1[CH2:9][CH:8]([O:10][C:11]2[C:20]3[C:15](=[CH:16][C:17]([O:21][CH3:22])=[CH:18][CH:19]=3)[N:14]=[C:13]([Cl:33])[CH:12]=2)[CH2:7][N:6]1[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:4]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178498521HCID 178498521, compound

Product 1

HCID 86618849HCID 86618849, compound

Conditions

Temperature
40 °C

Procedure

Crude 4-(2-hydroxy-7-methoxy-quinolin-4-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (3.18 g, 7.60 mmol) was dissolved in POCl3 (76 mL) and heated to 40° C. overnight. The reaction mixture was concentrated in vacuo and dissolved in CH2Cl2 (40 mL). 4 N HCl in 1,4-dioxane (40 mL) was added and stirred at r.t. for 1 h. The crude material was partitioned between H2O and CH2Cl2 and pH was adjusted to 11 with NaHCO3 and 1 N NaOH. The aqueous layer was extracted with CH2Cl2 (3×150 mL). The combined organic layer was dried with Na2SO4 and concentrated. The crude product was purified by combi-flash to give 2.05 g of 4-(2-Chloro-7-methoxy-quinolin-4-yloxy)-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. dissolutiondissolved in CH2Cl2 (40 mL)
  3. addition4 N HCl in 1,4-dioxane (40 mL) was added
  4. customThe crude material was partitioned between H2O and CH2Cl2 and pH
  5. extractionThe aqueous layer was extracted with CH2Cl2 (3×150 mL)
  6. dry with materialThe combined organic layer was dried with Na2SO4
  7. concentrationconcentrated
  8. customThe crude product was purified by combi-flash

Sources & evidence

ORD record
ord-27405107566f4c26aee3e4be4a19543c
Source dataset
uspto-grants-2011_02
Patent number
US07893264B2

Reaction notes

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