Isobutyric Acid → HCID 66690890, compound

HRID 592316Notes

Reaction equation

HRID 592316 reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:6][C:5]([C:15]([O:17][C@@H:18]([C:20]2[O:24][N:23]=[C:22]([CH3:25])[N:21]=2)[CH3:19])=[O:16])=[CH:4][C:3]=1[OH:26].[C:27](O)(=O)[CH:28]([CH3:30])[CH3:29].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ClC(Cl)(Cl)C#N>C(#N)C>[F:14][C:11]1[CH:12]=[CH:13][C:8]([C:7]2[C:2]3[N:1]=[C:27]([CH:28]([CH3:30])[CH3:29])[O:26][C:3]=3[CH:4]=[C:5]([C:15]([O:17][C@@H:18]([C:20]3[O:24][N:23]=[C:22]([CH3:25])[N:21]=3)[CH3:19])=[O:16])[CH:6]=2)=[CH:9][CH:10]=1

Participants

6

Reactant 4

HCID 6590Isobutyric AcidHCID 11011TrichloroacetonitrileHCID 11776TriphenylphosphineHCID 66691290HCID 66691290, compound

Product 1

HCID 66690890HCID 66690890, compoundYield 28.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of (1R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl 6-amino-4′-fluoro-5-hydroxybiphenyl-3-carboxylate (10.0 mg, 28.0 μmol), and isobutyric acid (4.94 mg, 56.0 μmol) and solid support triphenylphosphine (75% by weight; 29.4 mg, 84.0 μmol) in acetonitrile (0.28 mL) was added trichloroacetonitrile (5.63 μL, 56.0 μmol). The mixture was heated in a microwave reactor for 10 min at 150° C. The mixture was cooled to ambient temperature, filtered and concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% ammonium hydroxide) gave the title compound (3.3 mg). HRMS [M+1] found=409.1683.

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.05% ammonium hydroxide)

Sources & evidence

ORD record
ord-58343e25ba714c3cb4c9d3f6c26a1c6e
Source dataset
uspto-grants-2016_01
Patent number
US09238647B2

Reaction notes

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