Sodium Hydroxide → HCID 59833507, compound

HRID 1443890Notes

Reaction equation

HRID 1443890 reaction equation
[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=2)[C:16](O)=[O:17])=[N:4][NH:3]1.[NH:22]1[CH2:32][CH2:31][CH:25]([C:26]([O:28]CC)=[O:27])[CH2:24][CH2:23]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[OH-].[Na+]>O1CCCC1.O.CC(N(C)C)=O>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=2)[C:16]([N:22]2[CH2:23][CH2:24][CH:25]([C:26]([OH:28])=[O:27])[CH2:31][CH2:32]2)=[O:17])=[N:4][NH:3]1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 70770Ethyl 4-piperidinecarboxylateHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 251319063-((4-Oxo-3,4-dihydrophthalazin-1-yl)methyl)benzoic acid

Product 1

HCID 59833507HCID 59833507, compoundYield 65%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 31374DimethylacetamideSolvent

Procedure

3-(4-Oxo-3,4-dihydrophthalazin-1-ylmethyl)benzoic acid (A)(7.0 g, 0.25 mol), ethyl isonipecotate (5 ml, 0.32 mol), 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) (12.3 g, 0.32 mol) and N,N,-diisopropylethylamine (10.0 ml, 0.55 mol) were added to dimethylacetamide (40 ml) and stirred for 18 h. Water (100 ml) was added to the reaction mixture and the product was extracted into dichloromethane (4×50 ml). The combined organic layers were washed with water (3×100 ml), dried over MgSO4, filtered and evaporated in vacuo to yield an oil. To a solution of the oil in tetrahydrofuran (100 ml) was added 10% aqueous sodium hydroxide solution (20 ml) and the reaction was stirred for 18 hours. The reaction was concentrated, washed with ethyl acetate (2×30 ml) and acidified with 2M HCl to pH 2. The aqueous layer was extracted with dichloromethane (2×100 ml), then the extracts were dried over MgSO4, filtered and evaporated to yield 1-[3-(4-oxo-3,4-dihydrophthalazin-1-ylmethyl)benzoyl]piperidine-4-carboxylic acid (C) as a yellow solid (7.0 g, 65%), m/z [M+1]+ 392 (96% purity), δH 1.3-1.8 (5H, m), 2.8-3.1 (4H, m), 4.4 (2H, s), 7.2-7.3 (1H, m), 7.3-7.4 (1H, m), 7.7-8.0 (5H, m), 8.2-8.3 (1H, m), 12.6 (1H, s).

Workup

  1. extractionthe product was extracted into dichloromethane (4×50 ml)
  2. washThe combined organic layers were washed with water (3×100 ml)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customto yield an oil
  7. stirringthe reaction was stirred for 18 hours
  8. concentrationThe reaction was concentrated
  9. washwashed with ethyl acetate (2×30 ml)
  10. extractionThe aqueous layer was extracted with dichloromethane (2×100 ml)
  11. dry with materialthe extracts were dried over MgSO4
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-6c0d95a34cea40f99f035d3727f42069
Source dataset
uspto-grants-2010_02
Patent number
US07662818B2

Reaction notes

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