2-Nitrobenzenesulfonyl chloride → 17-Ethyl-1-hydroxy-12-[2'-(4"-(o-nitrophenylsulfonyloxy)-3"-propyloxycyclohexyl)-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 248253Notes

Reaction equation

HRID 248253 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]([CH3:55])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([OH:50])[CH:46]([O:51][CH2:52][CH2:53][CH3:54])[CH2:45]2)[CH:7]([CH3:56])[CH2:6][CH2:5][C:4]1=[O:57])[CH3:2].C(N(C(C)C)CC)(C)C.[N+:67]([C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][C:71]=1[S:76](Cl)(=[O:78])=[O:77])([O-:69])=[O:68]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[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]([CH3:55])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][S:76]([C:71]3[CH:72]=[CH:73][CH:74]=[CH:75][C:70]=3[N+:67]([O-:69])=[O:68])(=[O:77])=[O:78])[CH:46]([O:51][CH2:52][CH2:53][CH3:54])[CH2:45]2)[CH:7]([CH3:56])[CH2:6][CH2:5][C:4]1=[O:57])[CH3:2]

Participants

6

Reactant 3

HCID 155402-Nitrobenzenesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 5715218817-Ethyl-1-hydroxy-12-[2'-(4"-hydroxy-3"-n-propyloxycyclohexyl)-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

Product 1

HCID 5708934417-Ethyl-1-hydroxy-12-[2'-(4"-(o-nitrophenylsulfonyloxy)-3"-propyloxycyclohexyl)-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 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 17-ethyl-1-hydroxy-12-[2'-(4"-hydroxy-3"-n-propyloxycyclohexyl)-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 (130 mg, Example 50) in dry methylene chloride (2 ml) was added diisopropylethylamine (67 μl) followed by 2-nitrobenzenesulonyl chloride (72 mg), then 4-dimethylaminopyridine (47 mg). The yellow solution was stirred at room temperature under nitrogen atmosphere for 16 h, then quenched with sat'd aqueous sodium bicarbonate solution. The organic layer is washed (water, sat'd NaHCO3, sat'd NaCl), dried (anhydrous Na2SO4) and the solvent is removed in vacuo. Chromatography on silica gel gave 17-ethyl-1-hydroxy-12-[2'-[4"-(2"'-nitrobenzenesulfonyloxy)-3"-n-propyloxycyclohexyl]-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 as an off-white solid. This off-white solid (111 mg) was dissolved in dry DMF (1 ml) and to this solution was added sodium azide (32 mg) in one portion and heated at 80° C. under nitrogen atmosphere for 5.5 h. The reaction mixture was cooled, poured into water (5 ml) and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and purified by column chromatography on silica gel (2:1 ethyl acetate/hexane) to gave 52 mg of 17-ethyl-1-hydroxy-12-[2'-(4"-azido-3"-n-propyloxycyclohexyl)-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. This material (46 mg) and triphenylphosphine (29 mg) in 1 ml of wet benzene was refluxed for 6.5 h. The solvent was removed in vacuo and the residue was purified on silica gel column (eluted first with 5% MeOH/CH2Cl2, then 1% NH4OH in 5% MeOH/CH2Cl2) to give 37 mg of the title compound. MASS: (FAB) 803 (M+H).

Workup

  1. customquenched with sat'd aqueous sodium bicarbonate solution
  2. washThe organic layer is washed (water, sat'd NaHCO3, sat'd NaCl)
  3. dry with materialdried (anhydrous Na2SO4)
  4. customthe solvent is removed in vacuo

Sources & evidence

ORD record
ord-3dd24ed2c3e24dba96d910e2da1915bd
Source dataset
uspto-grants-1993_05
Patent number
US05208228

Reaction notes

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