Trifluoroacetic acid → Trifluoroacetic acid

HRID 85606노트

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HRID 85606 반응식
[O:1]=[S:2]1(=[O:51])[CH2:7][CH2:6][N:5]([CH2:8][C:9]([NH:11][C@:12]23[CH2:47][CH2:46][C@@H:45]([CH:48]([CH3:50])[CH3:49])[C@@H:13]2[C@@H:14]2[C@@:27]([CH3:30])([CH2:28][CH2:29]3)[C@@:26]3([CH3:31])[C@@H:17]([C@:18]4([CH3:44])[C@@H:23]([CH2:24][CH2:25]3)[C:22]([CH3:33])([CH3:32])[C:21]([C:34]3[CH:43]=[CH:42][C:37]([C:38]([O:40]C)=[O:39])=[CH:36][CH:35]=3)=[CH:20][CH2:19]4)[CH2:16][CH2:15]2)=[O:10])[CH2:4][CH2:3]1.[C:52]([OH:58])([C:54]([F:57])([F:56])[F:55])=[O:53].O.[OH-].[Li+]>C1COCC1.O>[O:51]=[S:2]1(=[O:1])[CH2:7][CH2:6][N:5]([CH2:8][C:9]([NH:11][C@:12]23[CH2:47][CH2:46][C@@H:45]([CH:48]([CH3:49])[CH3:50])[C@@H:13]2[C@@H:14]2[C@@:27]([CH3:30])([CH2:28][CH2:29]3)[C@@:26]3([CH3:31])[C@@H:17]([C@:18]4([CH3:44])[C@@H:23]([CH2:24][CH2:25]3)[C:22]([CH3:33])([CH3:32])[C:21]([C:34]3[CH:43]=[CH:42][C:37]([C:38]([OH:40])=[O:39])=[CH:36][CH:35]=3)=[CH:20][CH2:19]4)[CH2:16][CH2:15]2)=[O:10])[CH2:4][CH2:3]1.[C:52]([OH:58])([C:54]([F:57])([F:56])[F:55])=[O:53]

참가 물질

7

반응물 3

HCID 6422Trifluoroacetic acidHCID 168937Lithium hydroxide, monohydrateHCID 71245428methyl 4-[(1S,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-[[2-(1,1-dioxo-1,4-thiazinan-4-yl)acetyl]amino]-1-isopropyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]benzoate

생성물 2

HCID 6422Trifluoroacetic acid수율 54.1%HCID 683581304-((1S,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((1,1-dioxido-4-thiomorpholinyl)acetyl)amino)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-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 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
75 °C

실험 절차

To a solution of methyl 4-[(1S,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-[[2-(1,1-dioxo-1,4-thiazinan-4-yl)acetyl]amino]-1-isopropyl-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]benzoate, TFA (33 mg, 0.040 mmol) in THF (Volume: 3 mL) was added a 0.753 molar solution of lithium hydroxide monohydrate (0.316 mL, 0.158 mmol) in H2O. The reaction mixture was heated to 75° C. After 5.5 h, the reaction was concentrated to dryness. The crude residue was dissolved in THF (1.2 mL), MeOH (0.3 mL) and 1N HCl (0.2 mL). The solution was filtered and injected into reverse phase HPLC for purification using HPLC method 3 to give 4-((1S,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((1,1-dioxido-4-thiomorpholinyl)acetyl)amino)-1-isopropyl-5a,5b,8,8,11a-pentamethyl-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 (17.9 mg, 0.021 mmol, 54.1% yield) as a white solid. LCMS: m/z 707.6 (M+H+), retention time 2.030 min (method 6). 1H NMR (500 MHz, METHANOL-d4) δ=7.93 (d, J=8.5 Hz, 2H), 7.21 (d, J=8.5 Hz, 2H), 7.13 (s, 1H), 5.31 (dd, J=1.5, 6.1 Hz, 1H), 3.26-3.22 (m, 5H), 3.21-3.15 (m, 4H), 2.66-2.59 (m, 1H), 2.37 (dd, J=6.7, 12.5 Hz, 1H), 2.17 (dd, J=6.4, 17.1 Hz, 1H), 1.99-1.91 (m, 1H), 1.80-1.70 (m, 4H), 1.67-1.57 (m, 2H), 1.57-1.45 (m, 9H), 1.44-1.39 (m, 1H), 1.39-1.26 (m, 3H), 1.18-1.11 (m, 2H), 1.09 (s, 3H), 1.04 (s, 6H), 0.96 (s, 3H), 0.95 (s, 3H), 0.91 (d, J=7.0 Hz, 3H), 0.82 (d, J=6.7 Hz, 3H).

후처리

  1. concentrationthe reaction was concentrated to dryness
  2. dissolutionThe crude residue was dissolved in THF (1.2 mL)
  3. filtrationThe solution was filtered
  4. custominjected into reverse phase HPLC for purification

출처 및 근거

ORD 기록
ord-0ee1c699b9a24e7389f6ff25fa219f7d
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846647B2

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