Sodium Hydroxide → HCID 21914147, compound

HRID 551410Notes

Reaction equation

HRID 551410 reaction equation
C([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH2:6][CH:5]1[C:13]1[N:17]=[C:16]([CH2:18][CH2:19][CH3:20])[O:15][N:14]=1)(=O)C.[OH-].[Na+]>C(O)C.C(Cl)Cl>[CH2:18]([C:16]1[O:15][N:14]=[C:13]([CH:5]2[CH2:6][C:7]3[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=3)[NH:4]2)[N:17]=1)[CH2:19][CH3:20]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 21914106HCID 21914106, compound

Product 1

HCID 21914147HCID 21914147, compoundYield 56.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
57.5 °C

Procedure

A solution of compound 89 (0.0035 mole) in ethanol (60 ml) was treated with 3M NaOH (60 ml), and the reaction mix was heated to 55-60° C. for 5.5 hours. The reaction was rapidly cooled in an ice bath, diluted with DCM, and treated with cold distilled water. The layers were separated and the aqueous fraction was extracted three times with DCM. The organic fractions were combined, washed once with 1M NaOH, and dried over Na2SO4 and concentrated in vacuo. The residue was purified by prep column chromatography, yielding 0.45 g of 2,3-dihydro-2-(5-propyl-1,2,4-oxadiazol-3-yl)-1H-indole. b) A solution of 2,3-dihydro-2-(5-propyl-1,2,4-oxadiazol-3-yl)-1H-indole (0.0011 mole) in DCM (10 ml) was treated with N-methyl-N-(1-methylethyl)-2-propanamine (0.40 mL) then (2-fluoro-2-oxoethyl)-9H-fluoren-9-yl carbamic acid methyl ester (0.67 g). The reaction was stirred at room temperature for 40 hours and treated with another portion each of N-methyl-N-(1-methylethyl)-2-propanamine then (2-fluoro-2-oxoethyl)-9H-fluoren-9-yl carbamic acid methyl ester and stirred at room temperature for two days. The reaction was diluted with DCM, treated twice with saturated NaHCO3, and dried over Na2SO4. and concentrated. The residue was subjected to reverse phase prep column chromatography, yielding 0.35 g of 9H-fluoren-9-ylmethyl[2-[2,3-dihydro-2-(5-propyl-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]-2-oxoethyl]-carbamate. c) 9H-fluoren-9-ylmethyl[2-[2,3-dihydro-2-(5-propyl-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]-2-oxoethyl]-carbamate (0.35 g) was dissolved in DCM (40 ml), treated with piperidine (0.50 ml), and stirred at room temperature for 18 hours. The completed reaction was concentrated in vacuo and subjected to reverse phase prep column chromatograph, yielding 0.13 g of 2,3-dihydro-β-oxo-2-(5-propyl-1,2,4-oxadiazol-3-yl)-1H-indole-1-ethanamine trifluoroacetate (1:1) (compound 90, mp. 160-162° C.).

Workup

  1. additionthe reaction mix
  2. temperatureThe reaction was rapidly cooled in an ice bath
  3. additiontreated
  4. distillationwith cold distilled water
  5. customThe layers were separated
  6. extractionthe aqueous fraction was extracted three times with DCM
  7. washwashed once with 1M NaOH
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by prep column chromatography

Sources & evidence

ORD record
ord-2571817ded3440b0ad8fe0e488bc5694
Source dataset
uspto-grants-2011_05
Patent number
US07947713B2

Reaction notes

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