Potassium Carbonate → 2-{2-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-malonic acid dimethyl ester

HRID 2037377Notes

Reaction equation

HRID 2037377 reaction equation
[CH2:1]([C:3]1[CH:8]=[C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[C:17]([CH2:21][CH:22]([CH3:24])[CH3:23])=[CH:16][N:15]=3)[O:11][N:10]=2)[CH:6]=[C:5]([CH3:25])[C:4]=1[OH:26])[CH3:2].C([O-])([O-])=O.[K+].[K+].Cl[CH:34]([C:39]([O:41][CH3:42])=[O:40])[C:35]([O:37][CH3:38])=[O:36]>C(#N)C.CC(=O)OCC>[CH3:38][O:37][C:35](=[O:36])[CH:34]([O:26][C:4]1[C:5]([CH3:25])=[CH:6][C:7]([C:9]2[N:13]=[C:12]([C:14]3[CH:19]=[C:18]([CH3:20])[C:17]([CH2:21][CH:22]([CH3:23])[CH3:24])=[CH:16][N:15]=3)[O:11][N:10]=2)=[CH:8][C:3]=1[CH2:1][CH3:2])[C:39]([O:41][CH3:42])=[O:40]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 120070Dimethyl chloromalonateHCID 1363440752-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenol

Product 1

HCID 686304192-{2-Ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-malonic acid dimethyl esterYield 69.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of the compound of Example 32 (100 mg, 285 μmol) in acetonitrile (2 mL), K2CO3 (56 mg, 427 μmol) followed by dimethyl chloromalonate (57 mg, 341 μmol) is added. The mixture is stirred at 65° C. for 18 h. The mixture is diluted with EA and washed with water. The org. extract is concentrated and the crude product is purified on prep. TLC plates using heptane:EA 4:1 to give 2-{2-ethyl-4-[5-(5-isobutyl-4-methyl-pyridin-2-yl)-[1,2,4]oxadiazol-3-yl]-6-methyl-phenoxy}-malonic acid dimethyl ester (95 mg) as a colourless oil; LC-MS: tR=1.17 min, [M+H]+=482.01. This material (95 mg, 197 μmol) is dissolved in ethanol (10 mL) and treated with NaBH4 (60 mg, 1.58 mmol). The mixture is stirred at 60° C. for 1 h before the reaction is quenched with water. The mixture is extracted twice with EA and the combined extracts are concentrated. The crude product is purified on prep. TLC plates using heptane:EA 1:1 to give the title compound (44 mg) as a colourless oil; LC-MS: tR=1.02 min, [M+H]+=426.01; 1H NMR (CDCl3): δ1.00 (d, J=6.5 Hz, 6H), 1.31 (t, J=7.3 Hz, 3H), 1.95 (hept, J=6.3 Hz, 1H), 2.08 (t br, J=5.5 Hz, 2H), 2.42 (s, 3H), 2.47 (s, 3H), 2.63 (d, J=7.0 Hz, 2H), 2.80 (q, J=7.5 Hz, 2H), 3.91-4.05 (m, 4H), 4.19 (quint, J=4.5 Hz, 1H), 7.95 (s, 1H), 7.98 (s, 1H), 8.10 (s, 1H), 8.55 (s, 1H).

Workup

  1. additionis added
  2. washwashed with water
  3. extractionextract
  4. concentrationis concentrated
  5. customthe crude product is purified on prep

Sources & evidence

ORD record
ord-fdf9a71874924bc78955de01776ad3af
Source dataset
uspto-grants-2013_11
Patent number
US08575200B2

Reaction notes

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