Benzyl (diethoxyphosphoryl)acetate → 17-Ethyl-1-hydroxy-12-[2'-(4"-[benzyloxycarbonylmethylidenyl]-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 1079264Notes

Reaction equation

CC1C(C)=C(C)[SiH](C)[SiH-](C)(C)C=1.[Na+].C(OP([CH2:22][C:23]([O:25][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)=[O:24])(OCC)=O)C.C(=O)=O.C(#N)C.[CH2:39]([CH:41]1[CH:67]=[C:66]([CH3:68])[CH2:65][CH:64]([CH3:69])[CH2:63][CH:62]([O:70][CH3:71])[CH:61]2[O:72][C:57]([OH:76])([CH:58]([CH3:75])[CH2:59][CH:60]2[O:73][CH3:74])[C:56](=[O:77])[C:55](=[O:78])[N:54]2[CH:49]([CH2:50][CH2:51][CH2:52][CH2:53]2)[C:48](=[O:79])[O:47][CH:46]([C:80]([CH3:91])=[CH:81][CH:82]2[CH2:87][CH2:86][C:85](=O)[CH:84]([O:89][CH3:90])[CH2:83]2)[CH:45]([CH3:92])[CH:44]([O:93][Si:94]([C:97]([CH3:100])([CH3:99])[CH3:98])([CH3:96])[CH3:95])[CH2:43][C:42]1=[O:101])[CH3:40]>C1COCC1>[CH2:39]([CH:41]1[CH:67]=[C:66]([CH3:68])[CH2:65][CH:64]([CH3:69])[CH2:63][CH:62]([O:70][CH3:71])[CH:61]2[O:72][C:57]([OH:76])([CH:58]([CH3:75])[CH2:59][CH:60]2[O:73][CH3:74])[C:56](=[O:77])[C:55](=[O:78])[N:54]2[CH:49]([CH2:50][CH2:51][CH2:52][CH2:53]2)[C:48](=[O:79])[O:47][CH:46]([C:80]([CH3:91])=[CH:81][CH:82]2[CH2:87][CH2:86][C:85](=[CH:22][C:23]([O:25][CH2:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[O:24])[CH:84]([O:89][CH3:90])[CH2:83]2)[CH:45]([CH3:92])[CH:44]([O:93][Si:94]([C:97]([CH3:98])([CH3:99])[CH3:100])([CH3:96])[CH3:95])[CH2:43][C:42]1=[O:101])[CH3:40]

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 20 mL of a 1.0 M solution of sodium hexamethyldisilamide in THF was cooled to 0° C. in an ice bath under nitrogen. Then a solution of 5.85 g (20 mmole) of benzyl diethylphosphonoacetate in 10 mL of dry THF was added and the solution was stirred at 0° C. under nitrogen. After 15 min., the solution was cooled to -40° C. (dry ice-acetonitrile bath) under nitrogen, and 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 -40° C. under nitrogen. After 3 hr, the reaction was quenched by addition of 2 mL of glacial acetic acid in 10 mL of dry THF. Et2O was added and the mixture was partitioned between Et2O and water and the aqueous layer was washed with Et2O. The organic extracts were sequentially washed with saturated KHCO3 solution and brine, then the combined extract was dried over MgSO4, filtered and the filtrate was concentrated in vacuo. The oily residue was purified by flash chromatography (silica gel, 6 cm×20 cm) using ethyl acetate-hexane to afford 3.28 g (63%) of the title compound as a colorless foam; NMR (CDCl3) indicated about a 9:1 mixture of E::Z olefin isomers; MS (FAB) 1042 (M+Li).

Workup

stirringthe solution was stirred at -40° C. under nitrogen
waitAfter 3 hr
customthe reaction was quenched by addition of 2 mL of glacial acetic acid in 10 mL of dry THF
additionEt2O was added
customthe mixture was partitioned between Et2O and water
washthe aqueous layer was washed with Et2O
washThe organic extracts were sequentially washed with saturated KHCO3 solution and brine
extractionthe combined extract
dry with materialwas dried over MgSO4
filtrationfiltered
concentrationthe filtrate was concentrated in vacuo
customThe oily residue was purified by flash chromatography (silica gel, 6 cm×20 cm)

Sources & evidence

ORD record: ord-c8050a78ce4d44df9e0b23fb7ef4f49d
Source dataset: uspto-grants-1996_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05550233

Reaction notes

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