tert-Butanol → tert-Butyl 3-(3-(1-allyl-1H-1,2,3-triazol-4-yl)phenethoxy)propanoate

HRID 909920Notes

Reaction equation

HRID 909920 reaction equation
[CH:1]1(Br)[CH2:3][CH2:2]1.[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>[CH2:2]([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)[CH:1]=[CH2:3]

Participants

9

Reactant 4

HCID 6386tert-ButanolHCID 33557Sodium AzideHCID 78037BromocyclopropaneHCID 86641259Tert-butyl 3-(3-ethynylphenethoxy)propanoate

Product 1

HCID 59290465tert-Butyl 3-(3-(1-allyl-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
70 °C

Procedure

Cyclopropyl bromide (0.177 mL) was added in one portion to a mixture tert-butyl 3-(3-ethynylphenethoxy)propanoate [Example 4, Step ii)] (506 mg), sodium azid e (144 mg), tert-butanol (0.5 mL), water (2 mL) and copper(I) iodide (35.1 mg) and sealed into a microwave tube. The reaction was heated to 70° 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 (470 mg) as an oil. 1H NMR (400 MHz, CDCl3) δ 7.78 (s, 1H), 7.70 (s, 1H), 7.66 (d, J=7.9 Hz, 1H), 7.33 (t, J=7.7 Hz, 1H), 7.19 (d, J=7.7 Hz, 1H), 6.08 (ddt, J=5.9, 10.3 and 16.9 Hz, 1H), 5.41-5.32 (m, 2H), 5.03 (dt, J=6.2, 1.3 Hz, 2H), 3.70 (t, J=6.3 Hz, 2H), 3.69 (t, J=7.1 Hz, 2H), 2.92 (t, J=7.0 Hz, 2H), 2.48 (t, J=6.5 Hz, 2H), 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-3a602e44beb343259188e2d1cc6828b5
Source dataset
uspto-grants-2011_09
Patent number
US08017602B2

Reaction notes

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