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Methanol → ethyl 8-carbamoyl-6-(3-fluoro-4-methoxyphenyl)-9H-carbazole-2-carboxylate

HRID 2410873
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HRID 2410873 반응식
Br[C:2]1[CH:3]=[C:4]2[C:12](=[C:13]([C:15](=[O:17])[NH2:16])[CH:14]=1)[NH:11][C:10]1[CH:9]=[C:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:7]=[CH:6][C:5]2=1.[F:23][C:24]1[CH:25]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:27]=[CH:28][C:29]=1[O:30][CH3:31].C([O-])([O-])=O.[Na+].[Na+].CO>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[C:15]([C:13]1[CH:14]=[C:2]([C:26]2[CH:27]=[CH:28][C:29]([O:30][CH3:31])=[C:24]([F:23])[CH:25]=2)[CH:3]=[C:4]2[C:12]=1[NH:11][C:10]1[CH:9]=[C:8]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:7]=[CH:6][C:5]2=1)(=[O:17])[NH2:16]
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참가 물질

7

반응물 4

HCID 887MethanolHCID 10340Sodium CarbonateHCID 27590052-(3-Fluoro-4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 66604694ethyl 6-bromo-8-carbamoyl-9H-carbazole-2-carboxylate

생성물 1

HCID 66605361ethyl 8-carbamoyl-6-(3-fluoro-4-methoxyphenyl)-9H-carbazole-2-carboxylate수율 124.6%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매
HCID 1140Toluene용매

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온도
105 °C

실험 절차

A 250 ml pressure flask was loaded with ethyl 6-bromo-8-carbamoyl-9H-carbazole-2-carboxylate (1.39 g, 3.85 mmol, Example 58C), Pd(Ph3P)4 (280 mg, 0.242 mmol), 2-(3-fluoro-4-methoxyphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.30 g, 5.16 mmol), aqueous Na2CO3 (4.2 ml, 8.40 mmol), MeOH (21.00 ml) and Toluene (42 ml), flushed with nitrogen, sealed and heated to 105° C. for 4 hours in an oil bath. The reaction mixture was filtered and the collected solid washed with water. The filtrate was acidified with KHSO4 (1M solution in water) and extracted with dichloromethane. The organic layer was washed with brine, dried over MgSO4 and concentrated. The MgSO4 was washed with THF and a MeOH+CH2Cl2 mixture. All wash liquids, the extracted product and the collected solid residue were combined to give 1.95 g crude ethyl 8-carbamoyl-6-(3-fluoro-4-methoxyphenyl)-9H-carbazole-2-carboxylate. (estimated purity ˜75%). The crude product was used without further purification in the next reaction. MS (ESI) m/e−405 consistent with [M−H]− of product. HPLC retention time 2.13 min. (PHENOMENEX® Luna C18 S10, 3.0×50 mm column, 3 min gradient, 0-100% B, 4 mL/min. Solvent A: 5% CH3CN—95% H2O—10 mM NH4OAc; Solvent B: 95% CH3CN—5% H2O—10 mM NH4OAc), then isocratic at 100% B.

후처리

  1. customflushed with nitrogen
  2. customsealed
  3. filtrationThe reaction mixture was filtered
  4. washthe collected solid washed with water
  5. extractionextracted with dichloromethane
  6. washThe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. washThe MgSO4 was washed with THF

출처 및 근거

ORD 기록
ord-488988ddf97d4d6e9cf3d22be76597e4
출처 데이터셋
uspto-grants-2014_08
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08815840B2

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