Acetic Acid → 17-Ethyl-1,14-dihydroxy-12-[2'-(4"-(4"'-chlorophenyloxy)-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-tetraone

HRID 865554Notes

Reaction equation

HRID 865554 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].C(O)(=O)C.C(O)(=O)C.[Cl:65][C:66]1[CH:71]=[CH:70][C:69]([Bi](C2C=CC(Cl)=CC=2)C2C=CC(Cl)=CC=2)=[CH:68][CH:67]=1.C(O)(=O)C.C(=O)(O)O.ClC1C=CC([Bi](C2C=CC(Cl)=CC=2)C2C=CC(Cl)=CC=2)=CC=1>C(Cl)Cl.C([O-])(O)=O.[Na+].CC([O-])=O.CC([O-])=O.[Cu+2]>[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]([O:50][C:69]3[CH:70]=[CH:71][C:66]([Cl:65])=[CH:67][CH:68]=3)[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]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 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 86747380Tri(4-chlorophenyl)bismuth diacetateHCID 86747381Tri(4-chlorophenyl)bismuth carbonate

Product 1

HCID 5702868817-Ethyl-1,14-dihydroxy-12-[2'-(4"-(4"'-chlorophenyloxy)-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-tetraone

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred mixture 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-tetraone (150 mg, 0.189 mmol, 1 eq) and Cu(OAc)2 (6.1 mg, 0.033 mmol, 0.17 eq) in CH2Cl2 (2.5 ml) in a round bottom flask equipped with a magnetic stir-bar was added tri(4-chlorophenyl)bismuth diacetate [prepared immediately prior to use by addition of acetic acid (0.075 ml, 1.3 mmol, 6.9 eq) to a suspension of tri(4-chlorophenyl)bismuth carbonate (200 mg, 0.331 mmol, 1.75 eq) in CH2Cl2 (2.5 ml)]. The reaction flask was then fitted with a reflux condenser and the mixture warmed to 40° C. After 20 hours the reaction mixture was cooled, diluted with saturated aqueous NaHCO3 (10 mL) and extracted 4 times with CH2Cl2. The organic extracts were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The product was separated and purified two times by preparative TLC on silica gel (eluted with 2:1 hexanes/acetone) to give 40 mg 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(4"'-chlorophenyloxy)-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-tetraone. (1H NMR, 13C NMR, and mass spectral analysis were consistent with the desired structure).

Workup

  1. customequipped with a magnetic stir-bar
  2. customprepared immediately
  3. customThe reaction flask was then fitted with a reflux condenser
  4. temperatureAfter 20 hours the reaction mixture was cooled
  5. extractionextracted 4 times with CH2Cl2
  6. dry with materialThe organic extracts were dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe product was separated
  10. custompurified two times by preparative TLC on silica gel (eluted with 2:1 hexanes/acetone)

Sources & evidence

ORD record
ord-a024c931ff57411fbb76fe8ffddd82eb
Source dataset
uspto-grants-1996_10
Patent number
US05565560

Reaction notes

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