Morpholine → Ammonium Hydroxide

HRID 1734371Notes

Reaction equation

HRID 1734371 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]([CH3:60])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][CH2:51][CH2:52]OS(C)(=O)=O)[CH:46]([O:58][CH3:59])[CH2:45]2)[CH:7]([CH3:61])[CH:6]([O:62][Si:63]([C:66]([CH3:69])([CH3:68])[CH3:67])([CH3:65])[CH3:64])[CH2:5][C:4]1=[O:70])[CH3:2].[NH:71]1[CH2:76][CH2:75][O:74][CH2:73][CH2:72]1.[Na].N1CCOCC1.[H-].[Na+]>O1CCCC1>[OH-:9].[NH4+:16].[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]([CH3:60])=[CH:43][CH:44]2[CH2:49][CH2:48][CH:47]([O:50][CH2:51][CH2:52][N:71]3[CH2:76][CH2:75][O:74][CH2:73][CH2:72]3)[CH:46]([O:58][CH3:59])[CH2:45]2)[CH:7]([CH3:61])[CH:6]([O:62][Si:63]([C:66]([CH3:67])([CH3:68])[CH3:69])([CH3:64])[CH3:65])[CH2:5][C:4]1=[O:70])[CH3:2]

Participants

7

Reactant 4

HCID 8083MorpholineHCID 24758Sodium hydrideHCID 5728599317-Ethyl-1-hydroxy-14-(tert-butyldimethylsiloxy)-12-[2'-(4"-(2"'-methanesulfonyloxyethyloxy)-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-tetraoneHCID 67712922Sodium morpholine

Product 2

HCID 14923Ammonium HydroxideYield 2%HCID 5717026917-Ethyl-1-hydroxy-14-(tert-butyldimethylsiloxy)-12-[2'-(4"-(2"'-morpholinoethyloxy)-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 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
70 °C

Procedure

To a solution of 17-ethyl-1-hydroxy-14-(tert-butyldimethylsiloxy)-12-[2'-(4"-(2'"-methanesulfonyloxyethyloxy)-3"-methoxycyclohexyl)-1'-methylvinyl]-23,25-dimethoxy-13,1 9,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9 ]octacos-18-ene-2,3,10,16-tetraone (26.5 mg) in dry tetrahydofuran (0.3 mL) was added 200 μL of a sodium morpholine solution (prepared by addition of 10 μL morpholine to a suspension of 2.3 mg sodium hydride in 0.5 mL of tetrahydrofuran) and the mixture heated to 70° C. After 6 hours, the mixture is cooled to room temperature and quenched by the addition of saturated ammonium chloride solution, extracted with ethyl acetate, and the organic portion dried over magnesium sulfate. Purification of the concentrate by flash chromatography on silica gel (ethyl acetate:hexane (2:1)+1% methanol, then 2% ammonium hydroxide, 5% methanol, in methylene chloride) gave the title compound (10 mg). 1H NMR consistent with the desired structure.

Workup

  1. temperaturethe mixture is cooled to room temperature
  2. customquenched by the addition of saturated ammonium chloride solution
  3. extractionextracted with ethyl acetate
  4. dry with materialthe organic portion dried over magnesium sulfate
  5. customPurification of the
  6. concentrationconcentrate by flash chromatography on silica gel (ethyl acetate:hexane (2:1)+1% methanol

Sources & evidence

ORD record
ord-7ddf6a48d3184e4eae5afae1aabdd078
Source dataset
uspto-grants-1996_07
Patent number
US05532248

Reaction notes

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