Lithium hydroxide, monohydrate → (Z)-3-(2-Fluorophenyl)-2-(((2R,3S,4R,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)acrylic acid

HRID 1508420Notes

Reaction equation

HRID 1508420 reaction equation
C([O:4][C@@H:5]1[C@@H:10]([O:11]C(=O)C)[C@H:9]([O:15]C(=O)C)[C@@H:8]([O:19]/[C:20](/[C:29]([O:31]CC)=[O:30])=[CH:21]\[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[F:28])[O:7][C@H:6]1[CH2:34][O:35]C(=O)C)(=O)C.O[Li].O>C1COCC1.O>[F:28][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1/[CH:21]=[C:20](\[O:19][C@@H:8]1[C@@H:9]([OH:15])[C@H:10]([OH:11])[C@@H:5]([OH:4])[C@H:6]([CH2:34][OH:35])[O:7]1)/[C:29]([OH:31])=[O:30]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 66980300(2S,3S,4R,5S,6R)-2-(Acetoxymethyl)-6-(((Z)-3-ethoxy-1-(2-fluorophenyl)-3-oxoprop-1-en-2-yl)oxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate

Product 1

HCID 56959231(Z)-3-(2-Fluorophenyl)-2-(((2R,3S,4R,5R,6S)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)oxy)acrylic acidYield 87%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

The ester C4 (20 mg, 0.037 mmol) was dissolved in THF (0.4 mL) and added a solution of LiOH H2O (8.86 mg, 0.37 mmol) in water (0.3 mL). The reaction mixture was stirred at room temperature for one hour and then acidified until pH<3 with Dowex 50-X8 resin, filtered and concentrated, and the residue was purified by preparative HPLC using acetonitrile-water as an eluent. After freeze drying, the final product was isolated in 87% yield: 1H NMR (400 MHz, MeOH-d4): δ 8.31 (t, J=7.1 Hz, 1H), 7.24 (dd, J=13.6, 5.8 Hz, 1H), 7.14 (s, 1H), 7.07 (t, J=7.6 Hz, 1H), 7.03-6.96 (m, 1H), 5.17 (d, J=7.4 Hz, 1H), 3.66 (dd, J=12.0, 2.2 Hz, 1H), 3.52 (dd, J=12.0, 5.2 Hz, 1H), 3.41-3.23 (m, 3H), 3.17-3.11 (m, 1H); 13C NMR (101 MHz, MeOH-d4): δ 166.72, 161.83 (d, 1JC,F=249.7 Hz), 144.28, 132.66, 131.71, 125.15, 122.48, 115.93 (d, 1C), 115.78 (d, 1C), 102.66, 78.59, 78.07, 75.64, 71.35, 62.50; ESI-HRMS m/z: calcd for C15H17FO8Na+: 367.0800. found 367.0800.

Workup

  1. filtrationfiltered
  2. concentrationconcentrated
  3. customthe residue was purified by preparative HPLC
  4. customAfter freeze drying

Sources & evidence

ORD record
ord-bd8af646375842beb3900d465cd57551
Source dataset
uspto-grants-2015_12
Patent number
US09221860B2

Reaction notes

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