Acetic Acid → 17-Ethyl-1,14-dihydroxy-12-[2'-(4"-(4"'-fluorophenyloxy)-3"-methoxycyclohexyl)-1'-methyl-vinyl]-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 865553Notes

Reaction equation

HRID 865553 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.[F:65][C:66]1[CH:71]=[CH:70][C:69]([Bi](C2C=CC(F)=CC=2)C2C=CC(F)=CC=2)=[CH:68][CH:67]=1.C(O)(=O)C.C(=O)(O)O.FC1C=CC([Bi](C2C=CC(F)=CC=2)C2C=CC(F)=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]([F: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 11966511Acetic acid;tris(4-fluorophenyl)bismuthaneHCID 86747379Tri(4-fluorophenyl)bismuth carbonate

Product 1

HCID 5706466817-Ethyl-1,14-dihydroxy-12-[2'-(4"-(4"'-fluorophenyloxy)-3"-methoxycyclohexyl)-1'-methyl-vinyl]-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

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 (100 mg, 0.126 mmol, 1 eq) and Cu(OAc)2 (3 mg, 0.0165 mmol, 0.13 eq) in CH2Cl2 (1 ml) in a 4 mL screw-cap vial equipped with a magnetic stir-bar was added tri(4-fluorophenyl)bismuth diacetate [prepared immediately prior to use by addition of acetic acid (0.030 mL, 0.504 mmol, 4 eq) to a suspension of tri(4-fluorophenyl)bismuth carbonate (100 mg, 0.181 mmol, 1.4 eq) in CH2Cl2 (1 mL)]. The reaction vessel was capped and the mixture stirred for two days. The reaction mixture was diluted with several milliliters of saturated aqueous NaHCO3 and extracted 2 times with CH2Cl2. The organic extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The product was isolated by preparative TLC on silica gel (eluted with 3:1 hexanes/EtOAc) to afford 39 mg of 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(4"'-fluorophenyloxy)-3"-methoxycyclohexyl)-1'-methyl-vinyl]-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. customscrew-cap vial
  2. customequipped with a magnetic stir-bar
  3. customprepared immediately
  4. customThe reaction vessel was capped
  5. extractionextracted 2 times with CH2Cl2
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe product was isolated by preparative TLC on silica gel (eluted with 3:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-eb6f83c2b84640fb9e3ce40af81afaa2
Source dataset
uspto-grants-1996_10
Patent number
US05565560

Reaction notes

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