Methyl iodide → HCID 57424256, compound

HRID 1765840Notes

Reaction equation

HRID 1765840 reaction equation
[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:22]=[C:21]([O:23][CH:24]([CH3:26])[CH3:25])[C:20]3[C:19](=O)[CH2:18][CH2:17][C:16]([CH3:29])([CH3:28])[C:15]=3[CH:14]=2)=[CH:7][CH:6]=1.[CH:31]1([NH2:34])[CH2:33][CH2:32]1.[C:35]([BH3-])#N.[Na+].C(=O)([O-])[O-].[K+].[K+].CI>ClCCl.C(#N)C.O.C(=O)([O-])[O-].[Na+].[Na+].C(O)(=O)C>[CH3:1][O:2][C:3](=[O:30])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:22]=[C:21]([O:23][CH:24]([CH3:26])[CH3:25])[C:20]3[CH:19]([N:34]([CH:31]4[CH2:33][CH2:32]4)[CH3:35])[CH2:18][CH2:17][C:16]([CH3:28])([CH3:29])[C:15]=3[CH:14]=2)=[CH:7][CH:6]=1

Participants

11

Reactant 5

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 69828CyclopropylamineHCID 5003444Sodium cyanoborohydrideHCID 69073588HCID 69073588, compound2×

Product 1

HCID 57424256HCID 57424256, compoundYield 53%

Reagents, catalysts & solvents 5

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

A solution of {4-[8,8-dimethyl-5-oxo-4-(2-propoxy)-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-phenyl}-acetic acid methyl ester (Intermediate 128, 0.07 g, 0.187 mmol) in dichloromethane (3 mL) and acetonitrile (1.5 mL) was treated with cyclopropyl amine (1 mL, 14.45 mmol). After 5 minutes, acetic acid (1 mL) was added followed by sodium cyanoborohydride (0.12 g, 1.91 mmol). The reaction mixture was stirred overnight at ambient temperature. It was then diluted with water and saturated aqueous sodium carbonate solution and extracted with dichloromethane (×2). The combined organic extract was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to an oil. The oil was dissolved in acetone (15 mL) and treated with potassium carbonate (0.2 g, 1.45 mmol)-followed by methyl iodide (1-mL, 15.8 mmol) and the resulting reaction mixture was stirred overnight at ambient temperature. The precipitated solids were filtered off, the filtrate was evaporated in vacuo to a residue. Flash column chromatography over silica gel (230–400 mesh) using 2.5–6% ethyl acetate in hexane as the eluent afforded the title compound (0.045 g, 53%).

Workup

  1. extractionextracted with dichloromethane (×2)
  2. extractionThe combined organic extract
  3. dry with materialwas dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo to an oil
  6. dissolutionThe oil was dissolved in acetone (15 mL)
  7. stirringwas stirred overnight at ambient temperature
  8. filtrationThe precipitated solids were filtered off
  9. customthe filtrate was evaporated in vacuo to a residue

Sources & evidence

ORD record
ord-655e1b57e6464f4bbf7ae9fe4ce91da2
Source dataset
uspto-grants-2007_06
Patent number
US07226951B2

Reaction notes

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