Acetic Acid → 17-Ethyl-1,14-dihydroxy-12-[2'-(3"-(napth-2-yloxy)-4"-hydroxy-cyclohexyl)-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 1655772Notes

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]([CH3:52])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([OH:51])[CH2:45]2)[CH:7]([CH3:53])[CH:6]([OH:54])[CH2:5][C:4]1=[O:55])[CH3:2].C(O)(=O)C.C(O)(=O)C.[CH:64]1[C:73]2[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=2)[CH:67]=[CH:66][C:65]=1[Bi](C1C=CC2C(=CC=CC=2)C=1)C1C=CC2C(=CC=CC=2)C=1.C(O)(=O)C.C(=O)(O)O.C1C2C(=CC=CC=2)C=CC=1[Bi](C1C=CC2C(=CC=CC=2)C=1)C1C=CC2C(=CC=CC=2)C=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]([CH3:52])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([O:51][C:66]3[CH:65]=[CH:64][C:73]4[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=4)[CH:67]=3)[CH2:45]2)[CH:7]([CH3:53])[CH:6]([OH:54])[CH2:5][C:4]1=[O:55])[CH3:2]

Participants

Conditions

Temperature: 40 °C

Procedure

To a stirred mixture of 17-ethyl-1,14-dihydroxy-12-[2'-(3",4"-dihydroxycyclohexyl)-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 (250 mg, 0.32 mmol, 1 eq) and Cu(OAc)2 (10 mg, 0.055 mmol, 0.17 eq) in CH2Cl2 (5.5 ml) in a round bottom flask equipped with a magnetic stir-bar was added tri(2-naphthyl) bismuth diacetate [prepared immediately prior to use by addition of acetic acid (0.100 ml, 1.75 mmol, 5.46 eq) to a suspension of tri(2-naphthyl)bismuth carbonate (350 mg, 0.538 mmol, 1.7 eq) in CH2Cl2 (5.5 ml)]. The reaction flask was fitted with a reflux condenser and the mixture warmed to 40° C. for 4 hours then stirred at room temperature. After 3 days the reaction mixture was diluted with saturated aqueous NaHCO3 and extracted 3 times with CH2Cl2. The extracts were combined, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The products were separated and purified by preparative TLC on silica gel (eluted with 3:1 hexanes/acetone) to give 63 mg of 17-ethyl-1,14-dihydroxy-12-[2'-(3"-(napth-2-yloxy)-4"-hydroxycyclohexyl)-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 and 49 mg of 17-ethyl-1,14-dihyroxy-12-[2'-(4"-(naphth-2-yloxy)- 3"-hydroxycyclohexyl)-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 was consistent with the desired structure).

Workup

customequipped with a magnetic stir-bar
customprepared immediately
customThe reaction flask was fitted with a reflux condenser
extractionextracted 3 times with CH2Cl2
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
customThe products were separated
custompurified by preparative TLC on silica gel (eluted with 3:1 hexanes/acetone)

Sources & evidence

ORD record: ord-b3e5740e492b499d886f2776612666bd
Source dataset: uspto-grants-1993_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05250678

Reaction notes

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