Phenylacetone → 17-Ethyl-1-hydroxy-12-[2'-(4"-hydroxy-4"-[3-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 1079268Notes

Reaction equation

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>[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])([CH2:14][C:15](=[O:16])[CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[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]

Participants

Conditions

Temperature: -78 °C

Procedure

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., 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-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 (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 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:hexanes to afford 2.36 g (46%) of the title compound as a colorless foam; NMR (CDCl3) shows distinct AB pattern at 2.6 ppm; MS (FAB) 1044 (M+Li).

Workup

additionadded dropwise by canula to the first solution
additionwas added dropwise over 5 minutes
waitAfter 1 h
customthe reaction was quenched by addition of 2 mL of glacial acetic acid in 10 mL of dry tetrahydrofuran
additionEther was added
customthe mixture was partitioned between ether and water
washthe aqueous layer was washed with ether
washThe two ether extracts were sequentially washed with saturated KHCO3 solution and brine
extractionthe combined extract
dry with materialwas dried over MgSO4
filtrationfiltered
concentrationconcentrated
customThe oily residue was purified by HPLC (silica gel, Waters RCM)

Sources & evidence

ORD record: ord-fbbb2a36460f4e56a5c69fb9754ec240
Source dataset: uspto-grants-1996_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05550233

Reaction notes

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