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 57041962, compound

HRID 1939075Notes

Reaction equation

HRID 1939075 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](O)[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].B(F)(F)F.[CH3:61][CH2:62][O:63][CH2:64]C.[N+](=C[C:69]([O:71]CC)=[O:70])=[N-]>C(OCC)C>[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]([C:69]([O:71][CH2:64][O:63][CH2:62][CH3:61])=[O:70])[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

5

Reactant 3

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 8000Boron trifluoride etherateHCID 12192Ethyl diazoacetate

Product 1

HCID 57041962HCID 57041962, compoundYield 38.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a stirred solution 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 (200 mg, 0.253 mmol, 1 eq) in diethyl ether (6 mL) was added boron trifluoride etherate (0.009 mL, 0.073 mmol, 0.3 eq) and ethyl diazoacetate (0.080 mL, 0.760 mmol, 3 eq). The reaction mixture was stirred 12 h. The reaction mixture was quenched with saturated aqueous NaHCO3 and extracted 4× with CH2Cl2. The organic extracts were combined and dried over anhydrous Na2SO4. The mixture was filtered and concentrated in vacuo. The products were isolated by preparative TLC on silica gel (3:2 EtOAc/hexanes) and a second preparative TLC (eluted 2× with 3:1 hexanes/acetone) affording 24.7 mg of 17-ethyl-1,14-dihydroxy-12-[2'-(4"-(ethoxycarbomethoxy)-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. customThe reaction mixture was quenched with saturated aqueous NaHCO3
  2. extractionextracted 4× with CH2Cl2
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationThe mixture was filtered
  5. concentrationconcentrated in vacuo
  6. customThe products were isolated by preparative TLC on silica gel (3:2 EtOAc/hexanes)
  7. washa second preparative TLC (eluted 2× with 3:1 hexanes/acetone)

Sources & evidence

ORD record
ord-ee00d341cb884911b22b47bcfbf792f9
Source dataset
uspto-grants-1997_12
Patent number
US05693648

Reaction notes

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