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Lithium hydroxide, monohydrate → (2R,6S,13aS,14aR,16aS,Z)-2-(biphenyl-4-yl)-6-(tert-butoxycarbonylamino)-2-(butylthio)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid

HRID 1666533
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HRID 1666533 반응식
[C:1]1([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH:6]=[CH:5][C:4]([C@@:7]2([S:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH2:40][N:10]3[C:11](=[O:39])[C@@H:12]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:18]=[CH:19][C@@H:20]4[CH2:25][C@@:21]4([C:26]([O:28]CC)=[O:27])[NH:22][C:23](=[O:24])[C@@H:9]3[CH2:8]2)=[CH:3][CH:2]=1.O.[OH-].[Li+]>C1COCC1.CO.O>[C:1]1([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)[CH:2]=[CH:3][C:4]([C@@:7]2([S:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH2:40][N:10]3[C:11](=[O:39])[C@@H:12]([NH:31][C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH:18]=[CH:19][C@@H:20]4[CH2:25][C@@:21]4([C:26]([OH:28])=[O:27])[NH:22][C:23](=[O:24])[C@@H:9]3[CH2:8]2)=[CH:5][CH:6]=1
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참가 물질

6

반응물 2

HCID 168937Lithium hydroxide, monohydrate3회HCID 57988332(2R,6S,13aS,14aR,16aS,Z)-ethyl 2-(biphenyl-4-yl)-6-(tert-butoxycarbonylamino)-2-(butylthio)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate

생성물 1

HCID 57988333(2R,6S,13aS,14aR,16aS,Z)-2-(biphenyl-4-yl)-6-(tert-butoxycarbonylamino)-2-(butylthio)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid
수율 90.2%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매3회HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of (2R,6S,13aS,14aR,16aS,Z)-ethyl 2-(biphenyl-4-yl)-6-(tert-butoxycarbonylamino)-2-(butylthio)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylate (59 mg, 0.082 mmol) in THF (1 mL) and MeOH (1.000 mL) was added pre-made solution of Lithium hydroxide monohydrate (6.90 mg, 0.164 mmol) in water (1 mL). The resulting cloudy solution was stirred at room for 5 h. LC/MS analysis showed partial reaction. Another portion of Lithium hydroxide monohydrate (6.90 mg, 0.164 mmol) in water (0.2 ml) was added and stirred for additional 17 hours. LC/MS analysis showed there was still small portion of starting material remained. Another portion of Lithium hydroxide monohydrate (6.90 mg, 0.164 mmol) in water (0.2 ml) was added and stirred for additional 5 hours. Quenched with 5% citric acid, extracted with ethyl acetate. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated to afford the desired product (2R,6S,13aS,14aR,16aS,Z)-2-(biphenyl-4-yl)-6-(tert-butoxycarbonylamino)-2-(butylthio)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecine-14a-carboxylic acid (57 mg, 0.074 mmol, 90% yield) as a white foam. 1H NMR (500 MHz, MeOD) δ ppm 0.84 (t, J=7.32 Hz, 3 H) 1.14-1.37 (m, 5 H) 1.38-1.54 (m, 16 H) 1.53-1.68 (m, 4 H) 1.82-1.95 (m, 1 H) 1.96-2.12 (m, 1 H) 2.21-2.38 (m, 2 H) 2.42 (dt, J=12.21, 7.17 Hz, 1 H) 2.48-2.63 (m, 1 H) 2.84-3.00 (m, 1 H) 3.92-4.18 (m, 2 H) 4.49 (dd, J=10.38, 2.75 Hz, 1 H) 5.18 (d, J=10.68 Hz, 1 H) 5.35 (t, J=9.77 Hz, 1 H) 5.56-5.68 (m, 1 H) 7.30-7.39 (m, 1 H) 7.45 (t, J=7.63 Hz, 2 H) 7.55-7.63 (m, 4 H) 7.77 (d, J=8.24 Hz, 2 H). LC-MS (retention time: 3.34 min, method C), MS m/z 690(M+H).

후처리

  1. customreaction
  2. stirringstirred for additional 17 hours
  3. stirringstirred for additional 5 hours
  4. customQuenched with 5% citric acid
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-da95846156684f9cb1f0fed81d0926b8
출처 데이터셋
uspto-grants-2011_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08044023B2

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