Methyl iodide → HCID 69075764, compound

HRID 2377392Notes

Reaction equation

HRID 2377392 reaction equation
[CH3:1][O:2][C:3](=[O:35])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:22]=[C:21]([O:23][CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:20]3[C:19](=O)[CH2:18][CH2:17][C:16]([CH3:34])([CH3:33])[C:15]=3[CH:14]=2)=[CH:7][CH:6]=1.[CH:36]1([NH2:39])[CH2:38][CH2:37]1.[C:40]([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:35])[CH2:4][C:5]1[CH:6]=[CH:7][C:8]([C:11]#[C:12][C:13]2[CH:22]=[C:21]([O:23][CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:31])[CH3:29])[C:20]3[CH:19]([N:39]([CH:36]4[CH2:38][CH2:37]4)[CH3:40])[CH2:18][CH2:17][C:16]([CH3:34])([CH3:33])[C:15]=3[CH:14]=2)=[CH:9][CH:10]=1

Participants

11

Reactant 5

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 69828CyclopropylamineHCID 5003444Sodium cyanoborohydrideHCID 69072819HCID 69072819, compound2×

Product 1

HCID 69075764HCID 69075764, compoundYield 63%

Reagents, catalysts & solvents 5

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

Procedure

A solution of {4-[8,8-dimethyl-5-oxo-4-(2-trimethylsilanyl-ethoxymethoxy)-5,6,7,8-tetrahydro-naphthalen-2-ylethynyl]-phenyl}-acetic acid methyl ester (Intermediate 74, 0.905 g, 1.84 mmol) in dichloromethane (8 mL) and acetonitrile (4 mL) was treated with cyclopropyl amine (4 mL, 57.8 mmol). After 5 minutes, acetic acid (4 mL) was added followed by sodium cyanoborohydride (0.46 g, 7.32 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 (0.745 g, 5.4 mmol) followed by methyl iodide (1.2 mL, 19 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 2-20% ethyl acetate in hexane as the eluent afforded the title compound (0.6 g, 63%).

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. customthe resulting reaction mixture
  8. stirringwas stirred overnight at ambient temperature
  9. filtrationThe precipitated solids were filtered off
  10. customthe filtrate was evaporated in vacuo to a residue

Sources & evidence

ORD record
ord-a058856c5dcd49879f67e85d42484d0d
Source dataset
uspto-grants-2008_12
Patent number
US07468391B2

Reaction notes

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