Lithium hydroxide, monohydrate → HCID 25169516, compound

HRID 1175332Notes

Reaction equation

HRID 1175332 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]([C:19]2[CH:24]=[C:23]([CH2:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][CH2:33][CH3:34])=[CH:28][CH:27]=3)[C:22]([Cl:35])=[CH:21][C:20]=2[CH2:36][O:37][CH2:38][C:39]#[CH:40])[O:7][C@@H:6]1[CH2:41][O:42]C(=O)C)(=O)C.O[Li].O>C1COCC1.CO.O>[Cl:35][C:22]1[C:23]([CH2:25][C:26]2[CH:27]=[CH:28][C:29]([O:32][CH2:33][CH3:34])=[CH:30][CH:31]=2)=[CH:24][C:19]([C@H:8]2[C@H:9]([OH:15])[C@@H:10]([OH:11])[C@H:5]([OH:4])[C@@H:6]([CH2:41][OH:42])[O:7]2)=[C:20]([CH2:36][O:37][CH2:38][C:39]#[CH:40])[CH:21]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 86623487HCID 86623487, compound

Product 1

HCID 25169516HCID 25169516, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a stirred solution of (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-5-(4-ethoxybenzyl)-2-((prop-2-ynyloxy)methyl)phenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (prepared using methods analogous to those in Example 1 and Example 5 above, 251 mg, 0.39 mmol) in THF:MeOH:H2O (2:3:1, 6.0 mL) at 15° C., was added LiOH—H2O (19.7 mg, 0.47 mmol). After stirring for 12 h at room temperature, the reaction was complete, as indicated by HPLC. The reaction mixture was concentrated and the residue was dissolved in 20 mL of ethyl acetate. The organic layer was washed with brine (20 mL), 5% KHSO4 in brine (20 mL), dried over anhydrous sodium sulfate, evaporated, and the residue was purified by preparative TLC (PE:EtOAc:MeOH=8:80:1, Rf=0.45) to obtain 156 mg of title compound as a white solid (yield 84%; purity 99.2%, as determined by HPLC). 1H-NMR (CD3OD, 400 MHz) δ 7.48 (s, 1H), 7.42 (s, 1H), 7.11 (s, 4H), 4.86 (d, J=12.4 Hz, 1H), 4.60 (d, J=12.4 Hz, 1H), 4.52 (d, J=9.2 Hz, 1H), 4.20 (s, 2H), 4.12 (d, J=14.8 Hz, 1H), 4.06 (d, J=14.8 Hz, 1H), 3.98 (q, J=6.8 Hz, 2H), 3.86 (d, J=12.4 Hz, 1H), 3.70-3.66 (m, 1H), 3.52-3.41 (m, 4H), 2.63 (s, 1H), 1.36 (t, J=6.8 Hz, 3H); LC-MS (m/z) 477 [(M+1)+], 521 [(M+45)−].

Workup

  1. customat 15° C.
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in 20 mL of ethyl acetate
  4. washThe organic layer was washed with brine (20 mL), 5% KHSO4 in brine (20 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. customevaporated
  7. customthe residue was purified by preparative TLC (PE:EtOAc:MeOH=8:80:1, Rf=0.45)

Sources & evidence

ORD record
ord-50b84a7e12154b298de15f56b612ab22
Source dataset
uspto-grants-2010_11
Patent number
US07838498B2

Reaction notes

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