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

HRID 909913Notes

Reaction equation

HRID 909913 reaction equation
I[CH:2]([CH3:4])[CH3:3].[C:5]([C:7]1[CH:8]=[C:9]([CH:22]=[CH:23][CH:24]=1)[CH2:10][CH2:11][O:12][CH2:13][CH2:14][C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])#[CH:6].[N-:25]=[N+:26]=[N-:27].[Na+].C(O)(C)(C)C>C(OCC)(=O)C.N.[Cu]I.O>[CH:2]([N:25]1[CH:6]=[C:5]([C:7]2[CH:8]=[C:9]([CH:22]=[CH:23][CH:24]=2)[CH2:10][CH2:11][O:12][CH2:13][CH2:14][C:15]([O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:16])[N:27]=[N:26]1)([CH3:4])[CH3:3]

Participants

9

Reactant 4

HCID 6362Isopropyl iodideHCID 6386tert-ButanolHCID 33557Sodium AzideHCID 86641259Tert-butyl 3-(3-ethynylphenethoxy)propanoate

Product 1

HCID 67076107tert-Butyl 3-(3-(1-isopropyl-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 AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

2-Iodopropane (0.168 mL) was added in one portion to a mixture tert-butyl 3-(3-ethynylphenethoxy)propanoate [Example 4, Step ii)] (383 mg), sodium azide (109 mg), tert-butanol (0.75 mL), water (3 mL) and copper(I) iodide (26.6 mg) and sealed into a microwave tube. The reaction was heated to 80° C., over a period of 3 h in the microwave reactor. The reaction mixture was diluted with ethyl acetate and 35% ammonia (1 mL) and ethyl acetate (2 mL) were added. The mixture was stirred for 30 min. and extracted into ethyl acetate. The organic was evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 20 to 100% ethyl acetate in isohexane to afford the titled compound (291 mg) as an oil. 1H NMR (300 MHz, CDCl3) δ 7.79 (s, 1H), 7.72-7.64 (m, 2H), 7.33 (t, J=7.6 Hz, 1H), 7.18 (d, J=7.5 Hz, 1H), 4.89 (septet, J=6.6 Hz, 1H), 3.70 (t, J=6.4 Hz, 2H), 3.697 (t, J=7.3 Hz, 2H), 2.92 (t, J=7.1 Hz, 2H), 2.49 (t, J=6.4 Hz, 2H), 1.63 (d, J=6.7 Hz, 6H), 1.43 (s, 9H)

Workup

  1. customsealed into a microwave tube
  2. additionwere added
  3. extractionextracted into ethyl acetate
  4. customThe organic was evaporated
  5. customto afford crude product
  6. customThe crude product was purified by flash silica chromatography, elution gradient 20 to 100% ethyl acetate in isohexane

Sources & evidence

ORD record
ord-c67c14ae35d64213b0d0a023e3477736
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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