Methyl iodide → tert-Butyl 3-(3-(1-methyl-1H-1,2,3-triazol-4-yl)phenethoxy)propanoate

HRID 909895Notes

Reaction equation

HRID 909895 reaction equation
CI.[C:3]([C:5]1[CH:6]=[C:7]([CH:20]=[CH:21][CH:22]=1)[CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])#[CH:4].[N-:23]=[N+:24]=[N-:25].[Na+].[C:27](O)(C)(C)C>C(OCC)(=O)C.N.[Cu]I.O>[CH3:27][N:23]1[CH:4]=[C:3]([C:5]2[CH:6]=[C:7]([CH:20]=[CH:21][CH:22]=2)[CH2:8][CH2:9][O:10][CH2:11][CH2:12][C:13]([O:15][C:16]([CH3:18])([CH3:19])[CH3:17])=[O:14])[N:25]=[N:24]1

Participants

9

Reactant 4

HCID 6328Methyl iodideHCID 6386tert-ButanolHCID 33557Sodium AzideHCID 86641259Tert-butyl 3-(3-ethynylphenethoxy)propanoate

Product 1

HCID 67075980tert-Butyl 3-(3-(1-methyl-1H-1,2,3-triazol-4-yl)phenethoxy)propanoate

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 222AmmoniaSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

Methyl iodide (0.20 mL) was added in one portion to a mixture of tert-butyl 3-(3-ethynylphenethoxy)propanoate [Example 4, Step ii)] (682 mg), sodium azide (194 mg), tert-butanol (0.750 mL), water (3 mL) and copper (I) iodide (47 mg) and sealed into a microwave tube. The reaction was heated to 70° C., over a period of 2 h in the microwave reactor. The reaction mixture was diluted with ethyl acetate and 35% ammonia was added. The mixture was stirred for 30 min and separated. The organic layer was dried over magnesium sulfate, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20-100% ethyl acetate in isohexane then elution gradient 0-10% methanol in ethyl acetate to afford the subtitled compound (500 mg). 1H NMR (300 MHz, CDCl3) δ 7.77 (s, 1H), 7.70 (s, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.33 (t, J=7.7 Hz, 1H), 7.19 (d, J=7.7 Hz, 1H), 4.15 (s, 3H), 3.73-3.66 (m, 4H), 2.92 (t, J=7.0 Hz, 2H), 2.49 (t, J=6.4 Hz, 2H), 1.43 (s, 9H).

Workup

  1. customsealed into a microwave tube
  2. additionwas added
  3. customseparated
  4. dry with materialThe organic layer was dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto afford crude product
  8. customThe crude product was purified by flash silica chromatography, elution gradient 20-100% ethyl acetate in isohexane
  9. washelution gradient 0-10% methanol in ethyl acetate

Sources & evidence

ORD record
ord-5ea8aefa47dc436bafa06c363c62a8fe
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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