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Citric Acid → 3-Bromo-1-(4-fluorophenyl)-1h-1,2,4-triazole

HRID 1180639
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HRID 1180639 반응식
[Br:1][C:2]1[N:6]=[CH:5][NH:4][N:3]=1.[C:7]([OH:10])(=[O:9])[CH3:8].[C:11](O)(=O)[CH3:12].[F:15][C:16]1[CH:21]=[CH:20][C:19]([Bi]([C:30]2[CH:35]=[CH:34][C:33](F)=[CH:32]C=2)C2C=CC(F)=CC=2)=[CH:18][CH:17]=1.[CH3:37]N(C)C(N(C)C)=N.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCCC1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C(OCC)(=O)C.O>[C:7]([O:10][CH2:11][CH3:12])(=[O:9])[CH3:8].[CH3:30][CH2:35][CH2:34][CH:33]([CH3:32])[CH3:37].[F:15][C:16]1[CH:21]=[CH:20][C:19]([N:4]2[CH:5]=[N:6][C:2]([Br:1])=[N:3]2)=[CH:18][CH:17]=1
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참가 물질

10

반응물 4

HCID 311Citric AcidHCID 664601,1,3,3-TetramethylguanidineHCID 11966511Acetic acid;tris(4-fluorophenyl)bismuthaneHCID 178419478HCID 178419478, 화합물

생성물 2

HCID 21882781Isohexane ethyl acetate수율 40%HCID 235711323-Bromo-1-(4-fluorophenyl)-1h-1,2,4-triazole
수율 45%

시약·촉매·용매 4

HCID 8895Cupric acetate촉매HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

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온도
50 °C

실험 절차

A mixture of 3-bromo-1,2,4-1H-triazole (prepared as described in Chemische Berichte 1967, 100, 2250) (1.0 g, 6.76 mmol), tri(4-fluorophenyl)bismuth diacetate (prepared by the method described in Synthetic Communications 1996, 4569) (4.53 g, 7.4 mmol), copper (II) acetate (0.25 g, 20 mol %) and N,N,N′,N′-tetramethylguanidine (1.7 mL, 13.5 mmol) in dry tetrahydrofuran (30 mL) was stirred at 50° C. under a balloon of air for 16 hr. The suspension was poured into water (100 mL) and 1M citric acid (30 mL) to give a suspension of pH 3-4. Ethyl acetate (100 mL) was added and the mixture was filtered through Celite®, washing the filter cake with ethyl acetate (100 mL). The two phases of the filtrate were separated and the organic layer was dried (Na2SO4) and concentrated. Flash column chromatography on silica gel, eluting with 25% then 40% ethyl acetate—isohexane, gave 1-(4-fluorophenyl)-3-bromo-1,2,4-1H-triazole as an off-white solid (0.74 g, 45%). δ (1H, 400 MHz, CDCl3) 7.18-7.24 (2H, m), 7.60-7.65 (2H, m), 8.37 (1H, s). MS (ES+) 242, 244 ([MH]+). Step 2: [6S,9R,11R] 2′,3′,4′,5,5′,6,7,8,9,10-Decahydro-2-(1-(4-fluorophenyl)-1,2,4-triazol-3-yl)-5′-(2,2,2-trifluoroethyl)-spiro[6,9-methanobenzocyclooctene-11,3′-[1,2,5]thiadiazole] 1′,1′-dioxide

후처리

  1. customprepared by the method
  2. customto give
  3. additiona suspension of pH 3-4
  4. filtrationthe mixture was filtered through Celite®
  5. washwashing the filter cake with ethyl acetate (100 mL)
  6. customThe two phases of the filtrate were separated
  7. dry with materialthe organic layer was dried (Na2SO4)
  8. concentrationconcentrated
  9. washFlash column chromatography on silica gel, eluting with 25%

출처 및 근거

ORD 기록
ord-a23892edaaf5417a80a37de2404fb7b0
출처 데이터셋
uspto-grants-2007_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07282513B2

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