Phosphoric Acid → diisopropyl 6-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((benzyloxy)carbonyl)-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)spiro[3.3]hept-5-ene-2,2-dicarboxylate

HRID 1400977

反応式

HRID 1400977 の反応式
FC(F)(F)S(O[C:7]1[CH2:25][C:9]2([CH2:12][C:11]([C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20])([C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14])[CH2:10]2)[CH:8]=1)(=O)=O.C1([O-])C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:54][C@:55]12[C@@:72]3([CH3:73])[C@@H:63]([C@:64]4([CH3:84])[C@@H:69]([CH2:70][CH2:71]3)[C:68]([CH3:75])([CH3:74])[C:67](OS(C(F)(F)F)(=O)=O)=[CH:66][CH2:65]4)[CH2:62][CH2:61][C@@H:60]1[C@H:59]1[C@H:85]([C:88]([CH3:90])=[CH2:89])[CH2:86][CH2:87][C@:58]1([C:91]([O:93][CH2:94][C:95]1[CH:100]=[CH:99][CH:98]=[CH:97][CH:96]=1)=[O:92])[CH2:57][CH2:56]2.P(=O)(O)(O)O.[K]>C1(C)C=CC=CC=1.CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[CH2:94]([O:93][C:91]([C@:58]12[CH2:87][CH2:86][C@@H:85]([C:88]([CH3:90])=[CH2:89])[C@@H:59]1[C@@H:60]1[C@@:55]([CH3:54])([CH2:56][CH2:57]2)[C@@:72]2([CH3:73])[C@@H:63]([C@:64]3([CH3:84])[C@@H:69]([CH2:70][CH2:71]2)[C:68]([CH3:74])([CH3:75])[C:67]([C:7]2[CH2:25][C:9]4([CH2:10][C:11]([C:13]([O:15][CH:16]([CH3:18])[CH3:17])=[O:14])([C:19]([O:21][CH:22]([CH3:24])[CH3:23])=[O:20])[CH2:12]4)[CH:8]=2)=[CH:66][CH2:65]3)[CH2:62][CH2:61]1)=[O:92])[C:95]1[CH:100]=[CH:99][CH:98]=[CH:97][CH:96]=1

参加物

11

反応物 6

HCID 1004Phosphoric AcidHCID 11776TriphenylphosphineHCID 119047PhenolateHCID 5462222PotassiumHCID 54761067(1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(((trifluoromethyl)sulfonyl)oxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylateHCID 86692311HCID 86692311、化合物

生成物 1

HCID 86692326diisopropyl 6-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((benzyloxy)carbonyl)-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)spiro[3.3]hept-5-ene-2,2-dicarboxylate収率 21.4%

試薬・触媒・溶媒 4

HCID 178418476HCID 178418476、化合物触媒HCID 178418807HCID 178418807、化合物触媒HCID 1140Toluene溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

The following procedure was modified from J. Am. Chem. Soc. 2002, 124, 8001-8006. To a rbf containing diisopropyl 6-(((trifluoromethyl)sulfonyl)oxy)spiro[3.3]hept-5-ene-2,2-dicarboxylate (0.095 g, 0.229 mmol) was added bis(pinacolato)dibororon (0.064 g, 0.252 mmol), phenolate, K+(0.045 g, 0.344 mmol), triphenylphospine (3.61 mg, 0.014 mmol), and bis(triphenylphosphine)palladium(II) chloride (4.83 mg, 6.88 mmol). The mixture was diluted with toluene (2 mL), flushed with nitrogen, then was heated to 50° C. for 3 h. The mixture was cooled to rt and TLC showed all starting material had been consumed. To the mixture was added (1R,3aS,5aR,5bR,7aR,11aR,11bR,13aR,13bR)-benzyl 5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-9-(((trifluoromethyl)sulfonyl)oxy)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysene-3a-carboxylate (0.149 g, 0.220 mmol), phosphoric acid, potassium salt (0.146 g, 0.688 mmol) and PdCl2(dppf)-CH2Cl2 adduct (5.62 mg, 6.88 μmol). The mixture was diluted with DMF (2.000 mL), flushed with nitrogen, then was heated to 80° C. After heating the mixture for an additional 90 h, it was cooled to rt and was concentrated under reduced pressure, then was dissolved in DCM and MeOH and was filtered through a plug of silica gel and celite. The filtrate was concentrated under reduced pressure, and was purified by flash chromatography using a 0-25% ethyl acetate in hexanes gradient and a 12 g silica gel column. The major isolate from the purification contained a mixture of products, so it was further purified by flash chromatography using a slower, 0-5, 5-5, 5-10% ethyl acetate/hexanes gradient and a 12 g silica gel column. The fractions containing the expected product were combined and concentrated under reduced pressure to give diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((benzyloxy)carbonyl)-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)spiro[3.3]hept-5-ene-2,2-dicarboxylate (0.053 g, 0.047 mmol (based on 70% purity), 20.4% yield) as a colorless foam. 1H NMR (500 MHz, chloroform-d) δ=7.40-7.30 (m, 5H), 5.86 (s, 1H), 5.51 (dd, J=6.4, 1.8 Hz, 1H), 5.19-5.02 (m, 4H), 4.73 (d, J=1.5 Hz, 1H), 4.60 (s, 1H), 3.08-2.98 (m, 1H), 2.73-2.66 (m, 4H), 2.62-2.54 (m, 2H), 1.69 (s, 3H), 2.53-0.74 (m, 49H). The material was used in the next step with no additional purification.

後処理

  1. customflushed with nitrogen
  2. temperatureThe mixture was cooled to rt
  3. customhad been consumed
  4. customflushed with nitrogen
  5. temperaturewas heated to 80° C
  6. temperatureAfter heating the mixture for an additional 90 h
  7. temperatureit was cooled to rt
  8. concentrationwas concentrated under reduced pressure
  9. dissolutionwas dissolved in DCM
  10. filtrationMeOH and was filtered through a plug of silica gel and celite
  11. concentrationThe filtrate was concentrated under reduced pressure
  12. customwas purified by flash chromatography
  13. customThe major isolate from the purification
  14. additiona mixture of products
  15. customso it was further purified by flash chromatography
  16. additionThe fractions containing the expected product
  17. concentrationconcentrated under reduced pressure

出典と根拠

ORDレコード
ord-5a85458fb70f4504952759fa517213ce
出典データセット
uspto-grants-2014_12
特許番号
US08906889B2

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