Lithium hydroxide, monohydrate → HCID 56659829, compound

HRID 425056Notes

Reaction equation

HRID 425056 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]=[CH:23][C:22]([Cl:25])=[C:21]([CH2:26][C:27]3[CH:32]=[CH:31][C:30]([C:33]4([CH2:36][O:37][CH3:38])[CH2:35][CH2:34]4)=[CH:29][CH:28]=3)[CH:20]=2)[O:7][C@@H:6]1[CH2:39][O:40]C(=O)C)(=O)C.O[Li].O>C1COCC1.CO.O>[Cl:25][C:22]1[CH:23]=[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]([CH2:39][OH:40])[O:7]2)=[CH:20][C:21]=1[CH2:26][C:27]1[CH:28]=[CH:29][C:30]([C:33]2([CH2:36][O:37][CH3:38])[CH2:34][CH2:35]2)=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 57684698HCID 57684698, compound

Product 1

HCID 56659829HCID 56659829, compound

Reagents, catalysts & solvents 1

HCID 21892291Methanol tetrahydrofuran waterSolvent

Procedure

To a solution of the above crude (2R,3R,4R,5S,6S)-2-(acetoxymethyl)-6-(4-chloro-3-(4-(1-(methoxymethyl)cyclopropyl)benzyl)phenyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (intermediate BD) (25 mg) in THF:MeOH:H2O (2:3:1) (1 mL) was added LiOH.H2O (4.66 mg). After stirring for about 2.5 h, the volatiles were removed with a rotary evaporator. The residue was taken up with water (5 mL) and AcOEt (20 mL), the organic layer was separated, and the aqueous layer was extracted 3× with AcOEt. The combined organic phase was washed 1× with brine prior to drying over Na2SO4. Concentration and purification of the crude product by preparative HPLC afforded compound BE (7.5 mg). 1H NMR (CD3OD, 400 MHz) δ 7.35-7.33 (m, 2H), 7.27 (dd, J=8.0, 2.0 Hz, 1H), 7.21 (d, J=8.4 Hz, 2H), 7.10 (d, J=8.4 Hz, 2H), 4.11-4.01 (m, 3H), 3.87 (d, J=9.6 Hz, 1H), 3.70-3.66 (m, 1H), 3.48 (s, 2H), 3.45-3.34 (m, 4H), 3.26 (s, 3H), 0.83-0.82 (m, 4H); MS ESI (m/z): 449 (M+H)+, 466 (M+NH4)+, 493 (M+HCO2)−.

Workup

  1. customthe volatiles were removed with a rotary evaporator
  2. customthe organic layer was separated
  3. extractionthe aqueous layer was extracted 3× with AcOEt
  4. washThe combined organic phase was washed 1× with brine
  5. dry with materialto drying over Na2SO4
  6. concentrationConcentration and purification of the crude product by preparative HPLC
  7. customafforded compound

Sources & evidence

ORD record
ord-a461fde44c0f4f43adbe8b1e0b215109
Source dataset
uspto-grants-2012_01
Patent number
US08106021B2

Reaction notes

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