Trichloroacetonitrile → Methyl 2-fluoro-4-{5-[2'-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoate

HRID 219907노트

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HRID 219907 반응식
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.ClC(Cl)(Cl)C#N.[NH2:45][C:46](=[N:58]O)[C:47]1[CH:56]=[CH:55][C:50]([C:51]([O:53][CH3:54])=[O:52])=[C:49]([F:57])[CH:48]=1.CCN(C(C)C)C(C)C>C1COCC1>[F:57][C:49]1[CH:48]=[C:47]([C:46]2[N:45]=[C:13]([C:12]3[CH:11]=[CH:10][C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[C:2]([F:1])([F:19])[F:18])=[CH:17][CH:16]=3)[O:15][N:58]=2)[CH:56]=[CH:55][C:50]=1[C:51]([O:53][CH3:54])=[O:52]

참가 물질

7

반응물 5

HCID 11011TrichloroacetonitrileHCID 11776TriphenylphosphineHCID 81531DiisopropylethylamineHCID 27827142'-Trifluoromethyl (1,1'-biphenyl)-4-carboxylic acidHCID 76644654Methyl 4-[amino(hydroxyimino)methyl]-2-fluorobenzoate

생성물 1

HCID 67529078Methyl 2-fluoro-4-{5-[2'-(trifluoromethyl)biphenyl-4-yl]-1,2,4-oxadiazol-3-yl}benzoate수율 70%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
100 °C

실험 절차

In a microwave vial were added 4-(2-trifluoromethylphenyl)benzoic acid (Fluorochem, 53.2 mg; 0.20 mmol; 1 eq.), triphenylphosphine polymer bound (375 mg; 0.60 mmol; 3 eq.) and trichloroacetonitrile (30 μl; 0.30 mmol; 1.50 eq.). Anhydrous THF (2 mL) was added and the reaction vessel was sealed and heated to 100° C. for 5 min in the microwave. After cooling, the reaction vessel was uncapped and without filtering, Intermediate 1 (46.7 mg; 0.22 mmol; 1.10 eq.) in anhydrous THF (2 mL) was added to the solution along with DIEA (69 μl; 0.40 mmol; 2 eq.). The reaction was capped and heated at 150° C. for 15 min. After cooling, the reaction vessel was uncapped again and the resin was filtered, the filtrate passed through an NH2 SPE column (2 g) and washed by additional THF (2×2 mL). Solvents were evaporated, affording the title compound as a brown solid (61.9 mg; 70%). It was used in the next step without further purification. LC/MS (Method A): 443.3 (M+H)+. HPLC (Method A), Rt 5.98 min (Purity: 87.9%).

후처리

  1. customthe reaction vessel was sealed
  2. temperatureAfter cooling
  3. filtrationwithout filtering
  4. customThe reaction was capped
  5. temperatureheated at 150° C. for 15 min
  6. temperatureAfter cooling
  7. filtrationthe resin was filtered
  8. washwashed by additional THF (2×2 mL)
  9. customSolvents were evaporated

출처 및 근거

ORD 기록
ord-cf38cb242a1d4de1b3521303a53bc788
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202865B2

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