Water → HCID 57435808, compound

HRID 339461Notes

Reaction equation

HRID 339461 reaction equation
Cl[O:2][N:3]=[CH:4][C:5]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]([CH3:12])[CH:6]=1.C([O-])([O-])=O.[K+].[K+].[O:19]1[CH2:24][CH2:23][C:22](=[N:25][NH:26][C:27](=[O:37])[C:28]2[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[C:29]=2[CH3:36])[CH2:21][CH2:20]1.O>C(Cl)(Cl)Cl.C(Cl)Cl>[CH3:12][C:7]1[CH:6]=[C:5]([C:4]2[N:25]([NH:26][C:27](=[O:37])[C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([O:34][CH3:35])[C:29]=3[CH3:36])[C:22]3([CH2:21][CH2:20][O:19][CH2:24][CH2:23]3)[O:2][N:3]=2)[CH:10]=[C:9]([CH3:11])[CH:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 59016635HCID 59016635, compoundHCID 86594180HCID 86594180, compound

Product 1

HCID 57435808HCID 57435808, compoundYield 49%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
57.5 °C

Procedure

3,5-dimethyl-benzaldehyde chlorooxime (1.84 g, 4 mmol) was dissolved in 30 μL of CHCl3 in a round bottom flask. An aqueous solution of K2CO3 (25 mL, 0.166 g/mL) was added, followed by 1.05 g of 3-methoxy-2-methyl-benzoic acid (tetrahydro-pyran-4-ylidene)-hydrazide. The reaction was stirred overnight at 55-60° C. Water and CH2Cl2 (50 mL) were added, and the mixture was shaken in a separatory funnel. The aqueous phase was removed and extracted once with CHCl3 (25 mL). The organic phases were combined, washed once with dilute K2CO3, and dried over MgSO4. The solvent was removed in vacuo to yield 2.5 g of crude product. This material was triturated twice with 10% ether in hexane and then once with 25% ether in hexane. The solids were collected and filtered, yielding 720 mg of N-[3-(3,5-dimethyl-phenyl)-1,8-dioxa-2,4-diaza-spiro[4.5]dec-2-en-4-yl]-3-methoxy-2-methyl-benzamide at 80% purity and a 49% yield. 1H NMR (300 MHz, CDCl3) δ (ppm): 8.5 (s, 1H [NH]), 7.4 (s, 2H), 7.1 (m, 1H), 7.1 (s, 1H), 6.9 (d, 1H), 6.65 (d, 1H), 3.9 (m, 4H), 3.8 (s, 3H), 2.4 (m, 4H), 2.35 (s, 6H), 2.05 (s, 3H).

Workup

  1. stirringthe mixture was shaken in a separatory funnel
  2. customThe aqueous phase was removed
  3. extractionextracted once with CHCl3 (25 mL)
  4. washwashed once with dilute K2CO3
  5. dry with materialdried over MgSO4
  6. customThe solvent was removed in vacuo
  7. customto yield 2.5 g of crude product
  8. customThis material was triturated twice with 10% ether in hexane
  9. customThe solids were collected
  10. filtrationfiltered

Sources & evidence

ORD record
ord-dbe2cf10bc8e4bba81a5fbc92d73a885
Source dataset
uspto-grants-2014_11
Patent number
US08895306B2

Reaction notes

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