Water → HCID 118699718, compound

HRID 1773302Notes

Reaction equation

HRID 1773302 reaction equation
[CH2:1]1[CH2:10][N:9]([C:11]2[CH:12]=[C:13]([CH:18]=[CH:19][CH:20]=2)[C:14]([O:16]C)=[O:15])[CH2:8][C:7]2[CH:6]=[N:5][C:4]3[CH:21]=[CH:22][CH:23]=[CH:24][C:3]=3[C:2]1=2.[OH-].[Na+].O.O1CCCC1CO>CO.C(OCC)C.ClCCl.CO>[CH2:1]1[CH2:10][N:9]([C:11]2[CH:12]=[C:13]([CH:18]=[CH:19][CH:20]=2)[C:14]([OH:16])=[O:15])[CH2:8][C:7]2[CH:6]=[N:5][C:4]3[CH:21]=[CH:22][CH:23]=[CH:24][C:3]=3[C:2]1=2

Participants

8

Reactant 4

HCID 962WaterHCID 7360Tetrahydrofurfuryl alcoholHCID 14798Sodium HydroxideHCID 118699720HCID 118699720, compound

Product 1

HCID 118699718HCID 118699718, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 3283Diethyl EtherSolventHCID 21226129Dichloromethane methanolSolvent2×

Procedure

A 250 mL single-necked, round-bottomed flask was equipped with a magnetic stirrer and stir bar, 125 mL addition funnel, and a nitrogen inlet. To the flask was added a solution of methyl 3-(1,4-dihydrobenzo[c]-2,7-naphthyridin-3(2H)-yl)benzoate (6.0 g, 18.84 mmol) in methanol (60 mL). The stirred batch was treated drop-wise over 10 minutes with a solution of 3 N aqueous sodium hydroxide (38 mL) and methanol (30 mL). A yellow precipitate appeared and re-dissolved. The batch was stirred at ambient temperature for 18 hours. Solvent was removed under reduced pressure and the stirred aqueous residue was acidified to pH 6-7 with 3 N aqueous hydrochloric acid (˜38 mL). The resulting slurry was stirred at 23° C. for 2 hours. The solid was collected on a filter and rinsed with water (4 mL). More product was extracted from the filtrate with a 2:1 (v/v) mixture of 2-methyltetrahydro-furan-tetrahydrofuran (30×300 mL). The combined organic extracts were concentrated in vacuo to provide a residue. This residue was transferred to a small fritted glass funnel where it was swished consecutively with water (5 mL), 4:1 (v/v) tetrahydrofuran-methanol (20 mL), 8:1 (v/v) dichloromethane-methanol (8 mL), and 5:1 (v/v) dichloro-methane-methanol (9 mL), sucking the solvent through the frit each time. This material was then thoroughly mixed with the first crop and placed in a small fritted glass funnel. An final swish with diethyl ether (25 mL) was performed and the solid was dried at 23° C. in a vacuum oven to constant weight. In this way the title compound was obtained as a bright yellow solid (4.7 g, 83% yield) of >99 A % purity by HPLC analysis.

Workup

  1. customA 250 mL single-necked, round-bottomed flask was equipped with a magnetic stirrer
  2. additionbar, 125 mL addition funnel, and a nitrogen inlet
  3. dissolutionre-dissolved
  4. stirringThe batch was stirred at ambient temperature for 18 hours
  5. customSolvent was removed under reduced pressure
  6. stirringThe resulting slurry was stirred at 23° C. for 2 hours
  7. customThe solid was collected on
  8. filtrationa filter
  9. washrinsed with water (4 mL)
  10. extractionMore product was extracted from the filtrate with a 2:1 (v/v) mixture of 2-methyltetrahydro-furan-tetrahydrofuran (30×300 mL)
  11. concentrationThe combined organic extracts were concentrated in vacuo
  12. customto provide a residue
  13. customThis residue was transferred to a small fritted glass funnel
  14. additionThis material was then thoroughly mixed with the first crop
  15. customplaced in a small fritted glass funnel
  16. customthe solid was dried at 23° C. in a vacuum oven to constant weight

Sources & evidence

ORD record
ord-80622bad706c451480ab78fbc2bd2de8
Source dataset
uspto-grants-2016_02
Patent number
US09255096B1

Reaction notes

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