Trifluoroacetic acid → Trifluoroacetic acid

HRID 85611노트

반응식

HRID 85611 반응식
[F:1][C:2]1[CH:7]=[C:6]([CH2:8][NH:9][C@:10]23[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:11]2[C@@H:12]2[C@@:25]([CH3:28])([CH2:26][CH2:27]3)[C@@:24]3([CH3:29])[C@@H:15]([C@:16]4([CH3:42])[C@@H:21]([CH2:22][CH2:23]3)[C:20]([CH3:31])([CH3:30])[C:19]([C:32]3[CH:41]=[CH:40][C:35]([C:36]([O:38]C)=[O:37])=[CH:34][CH:33]=3)=[CH:18][CH2:17]4)[CH2:14][CH2:13]2)[CH:5]=[CH:4][N:3]=1.[C:49]([OH:55])([C:51]([F:54])([F:53])[F:52])=[O:50].O[Li].O>C1COCC1>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][NH:9][C@:10]23[CH2:45][CH2:44][C@@H:43]([C:46]([CH3:48])=[CH2:47])[C@@H:11]2[C@@H:12]2[C@@:25]([CH3:28])([CH2:26][CH2:27]3)[C@@:24]3([CH3:29])[C@@H:15]([C@:16]4([CH3:42])[C@@H:21]([CH2:22][CH2:23]3)[C:20]([CH3:31])([CH3:30])[C:19]([C:32]3[CH:41]=[CH:40][C:35]([C:36]([OH:38])=[O:37])=[CH:34][CH:33]=3)=[CH:18][CH2:17]4)[CH2:14][CH2:13]2)[CH:5]=[CH:4][N:3]=1.[C:49]([OH:55])([C:51]([F:54])([F:53])[F:52])=[O:50]

참가 물질

6

반응물 3

HCID 6422Trifluoroacetic acidHCID 168937Lithium hydroxide, monohydrateHCID 68358208methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoropyridin-4-yl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate

생성물 2

HCID 6422Trifluoroacetic acid수율 36.1%HCID 683582074-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoropyridin-4-yl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
75 °C

실험 절차

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoropyridin-4-yl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoate, TFA (77.7 mg, 0.101 mmol) in THF (3 mL) was added a 0.753 molar aqueous solution of LiOH.H2O (0.539 mL, 0.405 mmol). The reaction mixture was heated to 75° C. After 4 h, the reaction mixture was concentrated. The crude residue was dissolved in THF (1.5 mL) and MeOH (200 μL), filtered and purified by reverse phase preparative HPLC using HPLC method 3 to give 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-fluoropyridin-4-yl)methylamino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)benzoic acid, TFA (30.6 mg, 0.037 mmol, 36.1% yield) as a white solid. LCMS: m/e 637.7 (M−H)−, 3.12 min (method 6). 1H NMR (500 MHz, 1:1 CDCl3:MeOD) δ=8.24 (d, J=5.2 Hz, 1H), 7.92 (d, J=8.2 Hz, 2H), 7.43 (d, J=5.2 Hz, 1H), 7.24 (s, 1H), 7.20 (d, J=8.5 Hz, 2H), 5.29 (dd, J=1.7, 6.3 Hz, 1H), 4.78 (s, 1H), 4.17 (br. s., 2H), 2.78-2.69 (m, 1H), 2.18-2.10 (m, 2H), 2.09-2.01 (m, 2H), 1.98 (dd, J=3.1, 11.9 Hz, 1H), 1.96-1.88 (m, 1H), 1.83-1.76 (m, 1H), 1.72 (s, 3H), 1.70-1.64 (m, 1H), 1.63-1.40 (m, 10H), 1.39-1.31 (m, 1H), 1.31-1.23 (m, 2H), 1.13 (s, 3H), 1.07 (s, 3H), 1.02 (s, 3H), 0.95 (s, 3H), 0.94 (s, 3H). 13C NMR (1:1 CDCl3:MeOD) d ppm 15.3, 16.6, 17.4, 19.5, 20.6, 21.8, 22.2, 26.1, 27.6, 29.0, 29.5, 30.2, 33.9, 34.6, 37.2, 38.2, 38.4, 41.8, 42.8, 43.1, 45.7, 47.2, 49.7, 49.9, 50.3, 50.5, 53.9, 78.8, 123.1, 123.2, 124.9, 129.3, 129.7, 131.0, 147.4, 149.7, 164.0, 166.0, 170.1.

후처리

  1. concentrationthe reaction mixture was concentrated
  2. dissolutionThe crude residue was dissolved in THF (1.5 mL)
  3. filtrationMeOH (200 μL), filtered
  4. custompurified by reverse phase preparative HPLC

출처 및 근거

ORD 기록
ord-09171b72b3554738bf5b0a7ea46aac0b
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846647B2

반응 노트

불러오는 중…