Cesium carbonate → (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(3-cyclopropylprop-2-ynyloxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

HRID 425049Notes

Reaction equation

HRID 425049 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@H:13]([OH:14])[C@@H:12]([OH:15])[C@H:11]([OH:16])[C@@H:10]([CH2:17][OH:18])[O:9]2)=[CH:4][C:3]=1[CH2:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1C=CC(S(O[CH2:44][C:45]#[C:46][CH:47]2[CH2:49][CH2:48]2)(=O)=O)=CC=1>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C@H:13]([OH:14])[C@@H:12]([OH:15])[C@H:11]([OH:16])[C@@H:10]([CH2:17][OH:18])[O:9]2)=[CH:4][C:3]=1[CH2:19][C:20]1[CH:21]=[CH:22][C:23]([O:26][CH2:44][C:45]#[C:46][CH:47]2[CH2:49][CH2:48]2)=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 44580555Bms-5119262×HCID 576847003-Cyclopropylprop-2-ynyl 4-methylbenzenesulfonate

Product 1

HCID 25197294(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(3-cyclopropylprop-2-ynyloxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (intermediate D1) (20 mg, 0.0526 mmol) in 1 mL of DMF was added Cs2CO3 (21 ng, 0.063 mmol) and 3-cyclopropylprop-2-ynyl 4-methylbenzenesulfonate (intermediate AU) (20 mg, 0.079 mmol) at room temperature. After stirring for 2 h, the reaction was quenched with 1 mL of ice water. The mixture was extracted 3× with ethyl acetate (5 mL each). The combined organic layers were washed 2× with water (5 mL each) and brine prior to drying over Na2SO4. Concentration of the solution and purification of the crude product by preparative LC-MS afforded compound AV (10 mg). 1H NMR (CD3OD): δ 7.37˜7.34 (2H, m), 7.30˜7.28 (1H, dd, J=8.8, 2 Hz), 7.13˜7.11 (2H, d, J=8.8 Hz), 6.87˜6.83 (2H, d, J=8.8 Hz), 4.61 (2H, d, J=2 Hz), 4.11 (1H, d, J=9.2 Hz), 4.10˜4.04 (2H, dd, J=23.6, 14.8 Hz), 3.90˜3.87 (1H, m), 3.72˜3.68 (1H, m), 3.49˜3.39 (3H, m), 3.31˜3.28 (1H, m), 1.31˜1.24 (1H, m), 0.79˜0.75 (2H, m), 0.62˜0.59 (2H, m).

Workup

  1. customthe reaction was quenched with 1 mL of ice water
  2. extractionThe mixture was extracted 3× with ethyl acetate (5 mL each)
  3. washThe combined organic layers were washed 2× with water (5 mL each) and brine
  4. dry with materialto drying over Na2SO4
  5. customConcentration of the solution and purification of the crude product by preparative LC-MS
  6. customafforded compound AV (10 mg)

Sources & evidence

ORD record
ord-ce49be2f358449968074e38704ecfdc6
Source dataset
uspto-grants-2012_01
Patent number
US08106021B2

Reaction notes

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