Trichloroacetonitrile → 3-[3-(2-{[tert-Butyl(diphenyl)silyl]oxy}ethyl)-1,2,4-oxadiazol-5-yl]-6-chloro-2-methylpyridine

HRID 385962Notes

Reaction equation

HRID 385962 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[C:4]([CH3:11])[N:3]=1.ClC(Cl)(Cl)C#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Si:37]([O:54][CH2:55][CH2:56]/[C:57](=[N:59]/O)/[NH2:58])([C:50]([CH3:53])([CH3:52])[CH3:51])([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1.C(N(C(C)C)C(C)C)C>O1CCCC1>[Si:37]([O:54][CH2:55][CH2:56][C:57]1[N:59]=[C:6]([C:5]2[C:4]([CH3:11])=[N:3][C:2]([Cl:1])=[CH:10][CH:9]=2)[O:8][N:58]=1)([C:50]([CH3:53])([CH3:51])[CH3:52])([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)[C:38]1[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=1

Participants

7

Reactant 5

HCID 11011TrichloroacetonitrileHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 108548133-[tert-butyl(diphenyl)silyl]oxy-N'-hydroxypropanimidamideHCID 462238396-Chloro-2-methylpyridine-3-carboxylic acid

Product 1

HCID 595256053-[3-(2-{[tert-Butyl(diphenyl)silyl]oxy}ethyl)-1,2,4-oxadiazol-5-yl]-6-chloro-2-methylpyridine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
100 °C

Procedure

6-Chloro-2-methylnicotinic acid (Example 425, Step 1) (150 mg, 0.87 mmol) trichloroacetonitrile (0.13 ml, 1.31 mmol) and solid supported triphenylphosphine on polystyrene (1.88 mmol/g, 1.5 g, 2.62 mmol) were taken up in tetrahydrofuran (10.9 ml). The mixture was heated in the microwave at 100° C. for 5 minutes and cooled to room temperature. (1Z)-3-{[tert-Butyl(diphenyl)silyl]oxy}-N′-hydroxypropanimidamide (329 mg, 0.96 mmol), THF (5 mL), and N-ethyl-N-isopropylpropan-2-amine (0.15 ml, 0.87 mmol) were added. The resulting mixture was heated in the microwave at 150° C. for 15 minutes, cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and purified via silica gel chromatography (0-35% ethyl acetate in hexane) to afford the title compound.

Workup

  1. temperaturecooled to room temperature
  2. temperatureThe resulting mixture was heated in the microwave at 150° C. for 15 minutes
  3. temperaturecooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. custompurified via silica gel chromatography (0-35% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-c4dc398bd96f48b08c6bf537a316aaa5
Source dataset
uspto-grants-2013_02
Patent number
US08367706B2

Reaction notes

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