Trifluoroacetic acid → 3-Pyridineacetic Acid, (3aS,4R,7R,8S,9S,10R,11R,13R,15R,15aR)-10-[[2-O-Acetyl-3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl]oxy]-11-[[(3-cyano-1H-pyrrol-1-yl)carbonyl]oxy]-4-ethyltetradecahydro-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxo-2H-oxacyclotetradecino[4,3-d]oxazol-8-yl ester

HRID 2416556Notes

Reaction equation

HRID 2416556 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([O:10][C@@H:11]2[C@@H:27]([CH3:28])[C:26](=[O:29])[O:25][C@H:24]([CH2:30][CH3:31])[C@:23]3([CH3:32])[C@H:19]([NH:20][C:21](=[O:33])[O:22]3)[C@@H:18]([CH3:34])[C:17](=[O:35])[C@H:16]([CH3:36])[CH2:15][C@:14]([O:38][C:39]([NH2:41])=[O:40])([CH3:37])[C@H:13]([O:42][C@@H:43]3[O:52][C@H:51]([CH3:53])[CH2:50][C@H:49]([N:54]([CH3:56])[CH3:55])[C@H:44]3[O:45][C:46](=[O:48])[CH3:47])[C@H:12]2[CH3:57])=[O:9])[CH:2]=1.[CH:58]([CH:60]([CH2:63][CH:64](OC)OC)[C:61]#[N:62])=O.FC(F)(F)C(O)=O>CC#N.C(OCC)(=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]([O:10][C@@H:11]2[C@@H:27]([CH3:28])[C:26](=[O:29])[O:25][C@H:24]([CH2:30][CH3:31])[C@:23]3([CH3:32])[C@H:19]([NH:20][C:21](=[O:33])[O:22]3)[C@@H:18]([CH3:34])[C:17](=[O:35])[C@H:16]([CH3:36])[CH2:15][C@:14]([O:38][C:39]([N:41]3[CH:64]=[CH:63][C:60]([C:61]#[N:62])=[CH:58]3)=[O:40])([CH3:37])[C@H:13]([O:42][C@@H:43]3[O:52][C@H:51]([CH3:53])[CH2:50][C@H:49]([N:54]([CH3:55])[CH3:56])[C@H:44]3[O:45][C:46](=[O:48])[CH3:47])[C@H:12]2[CH3:57])=[O:9])[CH:2]=1

Participants

6

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 226308162-Formyl-4,4-dimethoxybutanenitrile2×HCID 600667223-Pyridineacetic Acid, (3aS,4R,7R,8S,9S,10R,11R,13R,15R,15aR)-10-[[2-O-Acetyl-3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl]oxy]-11-[(aminocarbonyl)oxy]4-ethyltetradecahydro-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxo-2H-oxacyclotetradecino[4,3-d]oxazol-8-yl Ester

Product 1

HCID 600667343-Pyridineacetic Acid, (3aS,4R,7R,8S,9S,10R,11R,13R,15R,15aR)-10-[[2-O-Acetyl-3,4,6-trideoxy-3-(dimethylamino)-beta-D-xylo-hexopyranosyl]oxy]-11-[[(3-cyano-1H-pyrrol-1-yl)carbonyl]oxy]-4-ethyltetradecahydro-3a,7,9,11,13,15-hexamethyl-2,6,14-trioxo-2H-oxacyclotetradecino[4,3-d]oxazol-8-yl esterYield 41.8%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of compound of Example 34 (0.35 g, 0.435 mmol) and 2-formyl-4,4-dimethoxy-butyronitrile (0.30 g, 1.91 mmol) in CH3CN was added trifluoroacetic acid (0.33 mL, 4.35 mmol). The mixture was heated to 60° C. for 18 hours and additional 2-formyl-4,4-dimethoxy-butyronitrile (0.15 g, 0.186 mmol) and trifluoroacetic acid (0.15 mL, 1.95 mmol) were added. The mixture is was heated to 60° C. for 18 hours before being cooled, diluted with ethyl acetate, washed with sat. aq. NaHCO3, water, brine, and dried over MgSO4. Concentration and chromatography (silica gel, 98:2:0.3 dichloromethane/methanol/conc. NH4OH) gave 0.16 g (41%) of the title compound. MS 880 (M+H)+.

Workup

  1. temperatureThe mixture is was heated to 60° C. for 18 hours
  2. temperaturebefore being cooled
  3. washwashed with sat. aq. NaHCO3, water, brine
  4. dry with materialdried over MgSO4
  5. concentrationConcentration and chromatography (silica gel, 98:2:0.3 dichloromethane/methanol/conc. NH4OH)

Sources & evidence

ORD record
ord-0c3b0cbe121243109c821cfbcec7dafe
Source dataset
uspto-grants-2004_11
Patent number
US06825172B2

Reaction notes

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