Acetic Anhydride → (3R,4S,5R,6R)-6-(acetoxymethyl)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triyl

HRID 2172700Notes

Reaction equation

HRID 2172700 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([CH2:13][C:14]3[CH:15]=[C:16]([C:21]4([O:31][C@H:30]([CH2:32][OH:33])[C@@H:28]([OH:29])[C@H:26]([OH:27])[C@H:24]4[OH:25])[O:22][CH3:23])[CH:17]=[CH:18][C:19]=3[CH3:20])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.CN1[CH2:40][CH2:39][O:38]CC1.C(O[C:45](=[O:47])[CH3:46])(=O)C>C1(C)C=CC=CC=1.C(OCC)(=O)C.CN(C)C1C=CN=CC=1>[C:21]([O:25][C@@H:24]1[C@@H:26]([O:27][C:24](=[O:25])[CH3:26])[C@H:28]([O:29][C:45](=[O:47])[CH3:46])[C@@H:30]([CH2:32][O:33][C:39](=[O:38])[CH3:40])[O:31][C:21]1([C:16]1[CH:17]=[CH:18][C:19]([CH3:20])=[C:14]([CH2:13][C:11]2[S:12][C:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)=[CH:9][CH:10]=2)[CH:15]=1)[O:22][CH3:23])(=[O:22])[CH3:16]

Participants

7

Reactant 3

HCID 7918Acetic AnhydrideHCID 79724-MethylmorpholineHCID 46930624(3R,4S,5S,6R)-2-(3-((5-(4-Fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-6-(hydroxymethyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triol

Product 1

HCID 46899467(3R,4S,5R,6R)-6-(acetoxymethyl)-2-(3-((5-(4-fluorophenyl)thiophen-2-yl)methyl)-4-methylphenyl)-2-methoxytetrahydro-2H-pyran-3,4,5-triyl

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of methyl 1-C-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methylphenyl)-D-glucopyranoside (net weight 10.54 g) in toluene and ethyl acetate was added N-methylmorpholine (11.9 g) and 4-dimethylaminopyridine (217 mg) at room temperature. The solution was cooled to 0° C. and acetic anhydride (52.7 mL) was added dropwise below 15° C. The reaction mixture was allowed to warm to room temperature and stirred for 15 hours. The mixture was quenched with 28% NH3 aqueous solution (ca. 31.6 mL) while maintaining pH range of 6 to 7. Water was added to the mixture and separated. The organic layer was washed with water and brine, dried over anhydrous MgSO4 and filtered. The filtrate was concentrated in vacuo to give methyl 2,3,4,6-tetra-O-acetyl-1-C-(3-{[5-(4-fluorophenyl)-2-thienyl]methyl}-4-methylphenyl)-D-glucopyranoside (17.59 g) as yellow oil.

Workup

  1. temperatureto warm to room temperature
  2. customThe mixture was quenched with 28% NH3 aqueous solution (ca. 31.6 mL)
  3. temperaturewhile maintaining pH range of 6 to 7
  4. additionWater was added to the mixture
  5. customseparated
  6. washThe organic layer was washed with water and brine
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-bd5555f8abf44beabf098562749ed52b
Source dataset
uspto-grants-2015_06
Patent number
US09056850B2

Reaction notes

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