2-((Tert-butyldimethylsilyl)oxy)acetaldehyde → methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(tert-butyldimethylsilyloxy)ethylamino)-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

HRID 85636

반응식

HRID 85636 반응식
[NH2:1][C@:2]12[CH2:37][CH2:36][C@@H:35]([C:38]([CH3:40])=[CH2:39])[C@@H:3]1[C@@H:4]1[C@@:17]([CH3:20])([CH2:18][CH2:19]2)[C@@:16]2([CH3:21])[C@@H:7]([C@:8]3([CH3:34])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:23])([CH3:22])[C:11]([C:24]2[CH:33]=[CH:32][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:26][CH:25]=2)=[CH:10][CH2:9]3)[CH2:6][CH2:5]1.[Si:41]([O:48][CH2:49][CH:50]=O)([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C([O-])(O)=O.[Na+].CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[Si:41]([O:48][CH2:49][CH2:50][NH:1][C@:2]12[CH2:37][CH2:36][C@@H:35]([C:38]([CH3:40])=[CH2:39])[C@@H:3]1[C@@H:4]1[C@@:17]([CH3:20])([CH2:18][CH2:19]2)[C@@:16]2([CH3:21])[C@@H:7]([C@:8]3([CH3:34])[C@@H:13]([CH2:14][CH2:15]2)[C:12]([CH3:22])([CH3:23])[C:11]([C:24]2[CH:25]=[CH:26][C:27]([C:28]([O:30][CH3:31])=[O:29])=[CH:32][CH:33]=2)=[CH:10][CH2:9]3)[CH2:6][CH2:5]1)([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42]

참가 물질

7

반응물 3

HCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehyde2회HCID 5049666Sodium triacetoxyborohydride2회HCID 68357865methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-1-isopropenyl-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)benzoate

생성물 1

HCID 86676599methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(2-(tert-butyldimethylsilyloxy)ethylamino)-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)benzoate수율 54.5%

시약·촉매·용매 3

HCID 11026Titanium isopropoxide촉매HCID 111,2-Dichloroethane용매HCID 516892Sodium Bicarbonate용매

실험 절차

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-amino-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 (300 mg, 0.552 mmol) in DCE (4 mL) was added (tert-butyldimethylsilyloxy)acetaldehyde (131 mL, 0.690 mmol) and titanium(IV) isopropoxide (0.202 mL, 0.690 mmol). The mixture was stirred at rt for 45 minutes and sodium triacetoxyborohydride (234 mg, 1.103 mmol) was added. The mixture was stirred at rt for 23 h and an additional 0.1 mL of (tert-butyldimethylsilyloxy)acetaldehyde and an additional 150 mg of sodium triacetoxyborohydride were added. The mixture was stirred at rt for an additional 22 h, then was diluted with 15 mL of sat. NaHCO3 and was extracted with dichloromethane (3×15 mL). The combined organic layers were dried with Na2SO4, the drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was adsorbed to silica gel and was purified by flash chromatography using a 0-10% EtOAc in hexanes gradient. The fractions containing the expected product were combined and were concentrated under reduced pressure to give the title compound (0.211 g, 0.301 mmol, 54.5% yield) as a clear yellow film. The product was used in the next step with no additional purification. LCMS: m/e 702.7 (M+H)+, 2.35 min (method 2).

후처리

  1. stirringThe mixture was stirred at rt for 23 h
  2. stirringThe mixture was stirred at rt for an additional 22 h
  3. extractionwas extracted with dichloromethane (3×15 mL)
  4. dry with materialThe combined organic layers were dried with Na2SO4
  5. customthe drying agent was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customwas purified by flash chromatography
  8. additionThe fractions containing the expected product
  9. concentrationwere concentrated under reduced pressure

출처 및 근거

ORD 기록
ord-5fb373ad81674be8a4108fea4a3fd465
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846647B2

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