Triethylamine → 1-{4'-[4-(3-Hydroxy-propyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester

HRID 1512606Notes

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:29](O)=[O:30])=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].C(N(CC)CC)C.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1.CCO.O>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:10]=[CH:11][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][CH2:29][OH:30])=[CH:17][CH:16]=3)=[CH:13][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

1-{4′-[4-(2-Carboxy-ethyl)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester (0.336 g, 0.8 mmol) and triethylamine (0.145 mL, 1.04 mmol) were dissolved in THF (6.6 mL) under N2 atmosphere and cooled to 0° C. Isobutyl chloroformate (0.126 mL, 0.96 mmol) was added and the reaction stirred for 40 minutes and was then filtered, rinsing with dioxane and THF, and the filtrate was collected and concentrated. The crude material was dissolved in THF (10 mL), H2O (4.4 mL), and EtOH (1.9 mL), and then sodium borohydride (0.176 g, 4.6 mmol) was added. The reaction was heated to 50° C. for five hours then cooled and submitted to standard aqueous workup. The residue was purified on silica gel (0-80% EtOAc in hexanes) to yield the title compound.

Workup

filtrationwas then filtered
washrinsing with dioxane and THF
customthe filtrate was collected
concentrationconcentrated
dissolutionThe crude material was dissolved in THF (10 mL)
temperatureThe reaction was heated to 50° C. for five hours
temperaturethen cooled
customThe residue was purified on silica gel (0-80% EtOAc in hexanes)

Sources & evidence

ORD record: ord-8a73b1141d844adbaf68a481f8c1a2a4
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08217066B2

Reaction notes

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