Sodium t-butoxide → HCID 86684922, 화합물

HRID 2402917노트

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HRID 2402917 반응식
[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([S:13]CCC(N)=O)=[C:9]([C:19]([F:22])([F:21])[F:20])[CH:8]=2)[CH:4]=[N:3]1.CC(C)([O-])C.[Na+].[C:29]([C:31]1([NH:34][C:35]([C@H:37]2[N:41]([C:42]([C:44]3([C:47]([F:50])([F:49])[F:48])[CH2:46][CH2:45]3)=[O:43])[CH2:40][C@@H:39](OS(C3C=CC=CC=3)(=O)=O)[CH2:38]2)=[O:36])[CH2:33][CH2:32]1)#[N:30]>O1CCCC1.CN(C)C(=O)C.O>[C:29]([C:31]1([NH:34][C:35]([C@@H:37]2[CH2:38][C@@H:39]([S:13][C:10]3[CH:11]=[CH:12][C:7]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)=[CH:8][C:9]=3[C:19]([F:21])([F:20])[F:22])[CH2:40][N:41]2[C:42]([C:44]2([C:47]([F:49])([F:50])[F:48])[CH2:46][CH2:45]2)=[O:43])=[O:36])[CH2:33][CH2:32]1)#[N:30]

참가 물질

7

반응물 3

HCID 23676156Sodium t-butoxideHCID 86684911HCID 86684911, 화합물HCID 86684916HCID 86684916, 화합물

생성물 1

HCID 86684922HCID 86684922, 화합물수율 111.8%

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 31374Dimethylacetamide용매2회

실험 절차

3-[4-(1-Methyl-1H-pyrazol-4-yl)-2-trifluoromethyl-phenylsulfanyl]-propionamide (16.3 g, 49.6 mmol) was dissolved in tetrahydrofuran (80 mL) before sodium tert-butoxide (4.7 g, 48.9 mmol) was added and the fine suspension was stirred for 2 h at room temperature. N,N-dimethylacetamide (40 mL) was added and the mixture was stirred for further 2.5 h at room temperature. A solution of benzenesulfonic acid (3S,5S)-5-(1-cyano-cyclopropylcarbamoyl)-1-(1-trifluoromethyl-cyclopropanecarbonyl)-pyrrolidin-3-yl ester (20 g, 42.4 mmol) in N,N-dimethylacetamide (40 mL) was added and the yellow, fine suspension was stirred for 42 h at room temperature. The mixture was diluted with water (240 mL) and extracted with tert-butyl methyl ether (1×160 mL, 3×80 mL). The combined organic extracts were washed with an aqueous sodium carbonate solution (1 M, 80 mL) and brine (80 mL), dried over sodium sulfate and concentrated in vacuo to yield the title compound as a light brown foam (27.1 g). The crude product (containing dimethylacetamide) was used in the next step without further purification. For characterization purposes, a 2 g sample of crude material was purified by column chromagraphy on silica gel (eluent: gradient ethyl acetate/heptane 4:1 (v/v) to ethyl acetate). Likewise, 1.7 g of purified material were obtained. MS (ESI & APCI): m/z=572.1 [M+H]+, 589.2 [M+NH4]+. 1H NMR (CDCl3, 600 MHz): δ 1.12-1.22 (m, 3H), 1.28-1.34 (m, 3H), 1.49-1.54 (m, 2H), 2.02 (ddd, J=5.6 Hz, 8.2 Hz, 13.6 Hz, 1H), 2.88 (ddd, J=5.7 Hz, 5.7 Hz, 13.7 Hz, 1H), 3.89-3.99 (m, 2H), 3.97 (s, 3H), 4.04-4.09 (m, 1H), 4.69 (dd, J=5.2 Hz, 8.2 Hz, 1H), 7.55 (d, J=8.2 Hz, 1H), 7.60 (bs, 1H), 7.62 (dd, J=1.8 Hz, 8.2 Hz, 1H), 7.69 (s, 1H), 7.77 (d, J=1.8 Hz, 1H), 7.79 (s, 1H).

후처리

  1. additionwas added
  2. stirringthe mixture was stirred for further 2.5 h at room temperature
  3. stirringthe yellow, fine suspension was stirred for 42 h at room temperature
  4. extractionextracted with tert-butyl methyl ether (1×160 mL, 3×80 mL)
  5. washThe combined organic extracts were washed with an aqueous sodium carbonate solution (1 M, 80 mL) and brine (80 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-8d8bd205eb784911bed87fbe6fcd5740
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08796471B2

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