17-Ethyl-1,14-dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-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-tetrone → HCID 54250165, compound

HRID 1974955Notes

Reaction equation

HRID 1974955 reaction equation
[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:53])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([O:51][CH3:52])[CH2:45]2)[CH:7]([CH3:54])[CH:6]([OH:55])[CH2:5][C:4]1=[O:56])[CH3:2].[CH3:57][Li]>C1COCC1>[CH2:1]([CH:3]1[CH:29]=[C:28]([CH3:30])[CH2:27][CH:26]([CH3:31])[CH2:25][CH:24]([O:32][CH3:33])[CH:23]2[O:34][C:19]([OH:38])([CH:20]([CH3:37])[CH2:21][CH:22]2[O:35][CH3:36])[C:18](=[O:39])[C:17](=[O:40])[N:16]2[CH:11]([CH2:12][CH2:13][CH2:14][CH2:15]2)[C:10](=[O:41])[O:9][CH:8]([C:42]([CH3:53])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([O:51][CH3:52])[CH2:45]2)[CH:7]([CH3:54])[CH:6]([OH:55])[CH2:5][C:4]1([OH:56])[CH3:57])[CH3:2]

Participants

4

Reactant 2

HCID 224117-Ethyl-1,14-dihydroxy-12-[1-(4-hydroxy-3-methoxycyclohexyl)prop-1-en-2-yl]-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-tetroneHCID 178418348HCID 178418348, compound

Product 1

HCID 54250165HCID 54250165, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 0.101 g (0.1 mmole) of 17-ethyl-1,14-dihydroxy-12-[2'-(4"-hydroxy-3"-methoxycyclohexyl)-1'-methylvinyl]-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-tetrone in 5 mL of dry THF was cooled to 0° C. under nitrogen. Then 1 mL of a 0.5M solution of methyllithium was added dropwise and the solution was stirred at -78° C. for 24 h. The solution was quenched at -78° C. by addition of 0.2 mL of glacial acetic acid and then diluted with 20 mL of ether and partitioned between ether and 1M KHCO3 solution. The ether layer was washed with 1M KHCO3 and brine, dried over MgSO4, and concentrated. The residue was dissolved in 2 mL of 1:9 48% aqueous HF-acetonitrile was stirred at room temperature for 8 h. The reaction was quenched by addition of 2 mL of ethoxytrimethylsilane and the solution was concentrated to dryness under vacuum. The residue was purified by flash chromatography (2×20 cm silica gel) using 25% acetone-hexane to afford 0.053 g (68%) of the title compound as a white solid.

Workup

  1. customThe solution was quenched at -78° C. by addition of 0.2 mL of glacial acetic acid
  2. additiondiluted with 20 mL of ether
  3. custompartitioned between ether and 1M KHCO3 solution
  4. washThe ether layer was washed with 1M KHCO3 and brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in 2 mL of 1:9 48% aqueous HF-acetonitrile
  8. stirringwas stirred at room temperature for 8 h
  9. customThe reaction was quenched by addition of 2 mL of ethoxytrimethylsilane
  10. concentrationthe solution was concentrated to dryness under vacuum
  11. customThe residue was purified by flash chromatography (2×20 cm silica gel)

Sources & evidence

ORD record
ord-8686e843ddaa413cb04de33685a3dde8
Source dataset
uspto-grants-1994_02
Patent number
US05284840

Reaction notes

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