Methanol → 1-(4-Fluoro-phenyl)4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazole-5-carbaldehyde

HRID 2307479

반응식

HRID 2307479 반응식
[Cl-].[CH3:2][O:3]C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].[F:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]2[C:49]3[CH:48]=[C:47]4[CH2:50][CH2:51][CH2:52][C:53](=O)[C:46]4([CH3:55])[CH2:45][C:44]=3[CH:43]=[N:42]2)=[CH:37][CH:36]=1.CO>C1COCC1.Cl.O>[F:34][C:35]1[CH:36]=[CH:37][C:38]([N:41]2[C:49]3[CH:48]=[C:47]4[CH2:50][CH2:51][CH2:52][CH:53]([CH:2]=[O:3])[C:46]4([CH3:55])[CH2:45][C:44]=3[CH:43]=[N:42]2)=[CH:39][CH:40]=1

참가 물질

8

반응물 4

HCID 887MethanolHCID 2723798Methoxymethyl-triphenylphosphonium chlorideHCID 3251421Potassium bis(trimethylsilyl)amideHCID 226059921-(4-Fluoro-phenyl)-4a-methyl-1,4,4a,6,7,8-hexahydro-benzo[f]indazol-5-one

생성물 1

HCID 226059711-(4-Fluoro-phenyl)4a-methyl-4,4a,5,6,7,8-hexahydro-1H-benzo[f]indazole-5-carbaldehyde수율 70.2%

시약·촉매·용매 3

HCID 313Hydrochloric Acid용매HCID 962Water용매HCID 8028Tetrahydrofuran용매3회

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온도
0 °C

실험 절차

To a cold (−30° C.) solution of (methoxymethyl)triphenylphosphonium chloride (13.85 g, 40.4 mmol) in THF (40 mL), was added KHMDS (0.5M in toluene, 70.8 mL, 35.4 mmol). The resulting red solution was stirred at 0° C. for 15 minutes before being treated with a solution of 205 (3 g, 10.1 mmol) in THF (40 mL). The mixture was stirred at room temperature for 24 hours. A solution of methanol in THF (1:1, 40 mL) and 4 N HCl (30 mL) was added to the mixture at 0° C. The resulting solution was allowed to stir at room temperature for 26 hours and was them poured into water (30 mL) and extracted with ether (4×50 mL). The combined organic layers were washed with brine, dried (MgSO4), and concentrated. Purification of the residue by flash chromatography on silica gel (0-50% ethyl acetate-hexanes) gave 2.2 g (70%) of 207 as a yellow solid. A small portion was further purified via bisulfite addition for characterization. 1H NMR (CDCl3) δ 1.12 (s, 3H), 1.35-1.49 (m, 1H), 1.67-1.8 (m, 1H), 1.87-2.0 (m, 2H), 2.28-2.48 (m, 3H), 2.9 (d, J=16.0 Hz, 1H), 3.1 (d, J=16.0 Hz, 1H), 6.18 (s, 1H), 7.16,(t, J=8.5 Hz, 2H), 7.42-7.48 (m, 3H), 9.90 (d, J=2.0 Hz, 1H); 13C NMR (CDCl3) 203.99, 162.64, 160.18, 147.26, 137.77, 136.35, 135.65, 135.62, 125.36, 125.32, 125.24, 116.09, 115.87, 113.36, 109.93, 60.78, 39.90, 34.55, 32.10, 24.52, 22.62, 18.96.

후처리

  1. stirringThe mixture was stirred at room temperature for 24 hours
  2. stirringto stir at room temperature for 26 hours
  3. extractionextracted with ether (4×50 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customPurification of the residue by flash chromatography on silica gel (0-50% ethyl acetate-hexanes)

출처 및 근거

ORD 기록
ord-b7fe136c2ca3437487e268ad7c2e9262
출처 데이터셋
uspto-grants-2004_12
특허 번호
US06831093B2

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