tert-Butanol → 1-{4'-[4-(2-Amino-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester

HRID 1528758Notes

Reaction equation

HRID 1528758 reaction equation
[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27][CH2:28]C(O)=O)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(O)(C)(C)C.C1(P([N:51]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:10]=[CH:11][C:12]([C:15]3[CH:16]=[CH:17][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[CH2:27][CH2:28][NH2:51])=[CH:19][CH:20]=3)=[CH:13][CH:14]=2)[CH2:7][CH2:8]1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6386tert-Butanol2×HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 665772681-{4'-[4-(2-Carboxy-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 665772451-{4'-[4-(2-Amino-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

1-{4′-[4-(2-Carboxy-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester (0.825 g, 1.97 mmol), tert-butanol (0.21 mL, 2.16 mmol), diphenylphosphoryl azide (0.47 mL, 2.16 mmol), and triethylamine (0.3 mL, 2.16 mmol) were combined in toluene (8 mL) and stirred at 100° C. for 4 hours. The reaction was cooled to 80° C. and additional tert-butanol (0.21 mL, 2.16 mmol) was added. After stirring overnight at 80° C., the reaction was cooled to room temperature and submitted to aqueous workup. The crude material was purified by silica gel chromatography (0-100% EtOAc in hexanes). Then, the isolated product was treated with 4 N HCl in 1,4-dioxane and stirred at 60° C. overnight. The solution was filtered and concentrated to give the title compound.

Workup

  1. temperatureThe reaction was cooled to 80° C.
  2. stirringAfter stirring overnight at 80° C.
  3. temperaturethe reaction was cooled to room temperature
  4. customThe crude material was purified by silica gel chromatography (0-100% EtOAc in hexanes)
  5. additionThen, the isolated product was treated with 4 N HCl in 1,4-dioxane
  6. stirringstirred at 60° C. overnight
  7. filtrationThe solution was filtered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-906309be4e7d4fa5a947d1a54d62c6ac
Source dataset
uspto-grants-2015_07
Patent number
US09090573B2

Reaction notes

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