Boron tribromide → 3-{2-Fluoro-4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one

HRID 2263444노트

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HRID 2263444 반응식
C([O:8][CH2:9][CH2:10][CH2:11][C:12]1[N:13]=[C:14]([C:32]2[CH:37]=[CH:36][C:35]([C:38]([F:41])([F:40])[F:39])=[CH:34][CH:33]=2)[S:15][C:16]=1[CH2:17][O:18][C:19]1[CH:24]=[CH:23][C:22]([C:25]2[NH:29][C:28](=[O:30])[O:27][N:26]=2)=[C:21]([F:31])[CH:20]=1)C1C=CC=CC=1.B(Br)(Br)Br.ClCCl.CC(C)=O.C([O-])(O)=O.[Na+]>ClCCl.CO>[F:31][C:21]1[CH:20]=[C:19]([O:18][CH2:17][C:16]2[S:15][C:14]([C:32]3[CH:37]=[CH:36][C:35]([C:38]([F:40])([F:41])[F:39])=[CH:34][CH:33]=3)=[N:13][C:12]=2[CH2:11][CH2:10][CH2:9][OH:8])[CH:24]=[CH:23][C:22]=1[C:25]1[NH:29][C:28](=[O:30])[O:27][N:26]=1

참가 물질

7

반응물 4

HCID 25134Boron tribromide2회HCID 516892Sodium BicarbonateHCID 21584124Propan-2-one--dichloromethane (1/1)HCID 1361499453-{4-[4-(3-Benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-phenyl}-4H-[1,2,4]oxadiazol-5-one

생성물 1

HCID 1361499883-{2-Fluoro-4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매3회

실험 절차

To a stirred solution of 100 mg of 3-{4-[4-(3-benzyloxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-2-fluoro-phenyl}-4H-[1,2,4]oxadiazol-5-one in 3 mL of dichloromethane at −70° C. was added 0.34 mL of a 1M solution of boron tribromide in dichloromethane. After 1 h at −60° C., TLC monitoring (dichloromethane/acetone 8/2) showed remaining starting material so 1 mL of a 1M solution of boron tribromide in dichloromethane was added. After 10 min, the reaction mixture was poured into 30 mL of methanol and was neutralised with 5 mL of a saturated aqueous solution of NaHCO3. The suspension was filtered and the filtrate was concentrated under reduced pressure. The residue was taken up into dichloromethane then water added. The aqueous layer was separated and extracted three times with dichloromethane. The combined organic layers were dried over magnesium sulfate, filtered and concentrated under reduced pressure to give 60 mg of crude product. Purification by column chromatography on silica gel (dichloromethane 1/acetone 1) gave 13 mg of a first batch of the title compound (purity >95%) and 50 mg of a second batch of the title compound (purity >90%). The second batch was repurified by column chromatography on silica gel (dichloromethane 90/methanol 10). A total of 48 mg of 3-{2-fluoro-4-[4-(3-hydroxy-propyl)-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethoxy]-phenyl}-4H-[1,2,4]oxadiazol-5-one was obtained.

후처리

  1. additionwas added
  2. waitAfter 10 min
  3. filtrationThe suspension was filtered
  4. concentrationthe filtrate was concentrated under reduced pressure
  5. additionwater added
  6. customThe aqueous layer was separated
  7. extractionextracted three times with dichloromethane
  8. dry with materialThe combined organic layers were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give 60 mg of crude product
  12. customPurification by column chromatography on silica gel (dichloromethane 1/acetone 1)

출처 및 근거

ORD 기록
ord-bc511209c51c42b1938ea29532701ecb
출처 데이터셋
uspto-grants-2010_12
특허 번호
US07851493B2

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