Phenylacetone → 17-Ethyl-1-hydroxy-12-[2'-(4"-hydroxy-4"-[1-phenyl-2-oxopropyl]-3"-methoxycyclohexyl)-1'-methylvinyl]-14-tert-butyldimethylsilyloxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone

HRID 1079269

반응식

HRID 1079269 반응식
CC1C(C)=C(C)[SiH](C)[SiH-](C)(C)C=1.[Na+].[CH3:14][C:15]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:16].[CH2:24]([CH:26]1[CH:52]=[C:51]([CH3:53])[CH2:50][CH:49]([CH3:54])[CH2:48][CH:47]([O:55][CH3:56])[CH:46]2[O:57][C:42]([OH:61])([CH:43]([CH3:60])[CH2:44][CH:45]2[O:58][CH3:59])[C:41](=[O:62])[C:40](=[O:63])[N:39]2[CH:34]([CH2:35][CH2:36][CH2:37][CH2:38]2)[C:33](=[O:64])[O:32][CH:31]([C:65]([CH3:76])=[CH:66][CH:67]2[CH2:72][CH2:71][C:70](=[O:73])[CH:69]([O:74][CH3:75])[CH2:68]2)[CH:30]([CH3:77])[CH:29]([O:78][Si:79]([C:82]([CH3:85])([CH3:84])[CH3:83])([CH3:81])[CH3:80])[CH2:28][C:27]1=[O:86])[CH3:25]>O1CCCC1.ClCCl.[Cl-].C(O[Ti+](OC(C)C)OC(C)C)(C)C>[CH2:24]([CH:26]1[CH:52]=[C:51]([CH3:53])[CH2:50][CH:49]([CH3:54])[CH2:48][CH:47]([O:55][CH3:56])[CH:46]2[O:57][C:42]([OH:61])([CH:43]([CH3:60])[CH2:44][CH:45]2[O:58][CH3:59])[C:41](=[O:62])[C:40](=[O:63])[N:39]2[CH:34]([CH2:35][CH2:36][CH2:37][CH2:38]2)[C:33](=[O:64])[O:32][CH:31]([C:65]([CH3:76])=[CH:66][CH:67]2[CH2:72][CH2:71][C:70]([OH:73])([CH:17]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:15](=[O:16])[CH3:14])[CH:69]([O:74][CH3:75])[CH2:68]2)[CH:30]([CH3:77])[CH:29]([O:78][Si:79]([C:82]([CH3:83])([CH3:84])[CH3:85])([CH3:81])[CH3:80])[CH2:28][C:27]1=[O:86])[CH3:25]

참가 물질

7

반응물 3

HCID 7678PhenylacetoneHCID 5718775817-Ethyl-1-hydroxy-12-[2'-(4"-oxo-3"-methoxycyclohexyl)-1'-methylvinyl]-14-t-butyldimethylsilyloxy-23,25-dimethoxy-13,19, 21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos 18-ene-2,3,10,16-tetraoneHCID 131719515Sodium hexamethyldisilamide

생성물 1

HCID 5721639917-Ethyl-1-hydroxy-12-[2'-(4"-hydroxy-4"-[1-phenyl-2-oxopropyl]-3"-methoxycyclohexyl)-1'-methylvinyl]-14-tert-butyldimethylsilyloxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetraone수율 61%

시약·촉매·용매 3

HCID 3084342Chlorotitanium triisopropoxide촉매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
-78 °C

실험 절차

A solution of 20 mL of a 1.0M solution of sodium hexamethyldisilamide in tetrahydrofuran was cooled to -78° C. in an ice bath under nitrogen. Then a solution of 3.0 g (20 mmole) of benzyl methyl ketone in 10 mL of dry THF was cooled to -78° C. and added dropwise by canula to the first solution. After 5 min., 20 mL of a 1M solution of triisopropoxytitanium chloride in dichloromethane was added and the solution grew deep orange. After 10 min., a pre-cooled (-78° C.) solution of 4.5 g (5 mmole) of 17-ethyl-1-hydroxy-12-[2'-(4"-oxo-3"-methoxycyclohexyl)-1'-methylvinyl]-14-t-butyl-dimethylsilyloxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (Example 9) in 10 mL of dry tetrahydrofuran was added dropwise over 5 minutes and the solution was stirred at -78° C. under nitrogen. After 1 h, the reaction was quenched by addition of 2 mL of glacial acetic acid in 10 mL of dry tetrahydrofuran. Ether was added and the mixture was partitioned between ether and water. The cloudy mixture was filtered through Celite and the aqueous layer was washed with ether. The two ether extracts were sequentially washed with saturated KHCO3 solution and brine, then the combined extract was dried over MgSO4, filtered and concentrated. The oily residue was purified by HPLC (silica gel, Waters RCM) using 1:3:6 acetonitrile:methyl-tert-butylether:hexane to afford 3.15 g (61%) of the title compound as a colorless foam; NMR (CDCl3) shows singlet at 2.1 ppm; MS (FAB) 1044 (M+Li).

후처리

  1. additionadded dropwise by canula to the first solution
  2. waitAfter 10 min.
  3. additionwas added dropwise over 5 minutes
  4. waitAfter 1 h
  5. customthe reaction was quenched by addition of 2 mL of glacial acetic acid in 10 mL of dry tetrahydrofuran
  6. additionEther was added
  7. customthe mixture was partitioned between ether and water
  8. filtrationThe cloudy mixture was filtered through Celite
  9. washthe aqueous layer was washed with ether
  10. washThe two ether extracts were sequentially washed with saturated KHCO3 solution and brine
  11. extractionthe combined extract
  12. dry with materialwas dried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe oily residue was purified by HPLC (silica gel, Waters RCM)

출처 및 근거

ORD 기록
ord-b1c29e2579054f2480e34931c1970918
출처 데이터셋
uspto-grants-1996_08
특허 번호
US05550233

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