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

HRID 425076Notes

Reaction equation

HRID 425076 reaction equation
CC1C=CC(S(O[CH2:12][CH2:13][O:14][CH2:15][CH2:16][F:17])(=O)=O)=CC=1.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C@H:25]2[C@H:30]([OH:31])[C@@H:29]([OH:32])[C@H:28]([OH:33])[C@@H:27]([CH2:34][OH:35])[O:26]2)=[CH:21][C:20]=1[CH2:36][C:37]1[CH:42]=[CH:41][C:40]([OH:43])=[CH:39][CH:38]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)C>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C@H:25]2[C@H:30]([OH:31])[C@@H:29]([OH:32])[C@H:28]([OH:33])[C@@H:27]([CH2:34][OH:35])[O:26]2)=[CH:21][C:20]=1[CH2:36][C:37]1[CH:38]=[CH:39][C:40]([O:43][CH2:12][CH2:13][O:14][CH2:15][CH2:16][F:17])=[CH:41][CH:42]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 44580555Bms-5119262×HCID 595577772-(2-Fluoroethoxy)ethyl 4-methylbenzenesulfonate

Product 1

HCID 25197071(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-(2-(2-fluoroethoxy)ethoxy)benzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triolYield 6.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

2-(2-fluoroethoxy)ethyl 4-methylbenzenesulfonate (52 mg, 0.19 mmol) dissolved in anhydrous DMF (3 mL) was added to a flask containing (2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (intermediate D1) (57 mg, 0.15 mmol) in DMF (3 mL) at room temperature. Cesium carbonate (0.12 g, 0.36 mmol) was added to the flask, and the resulting mixture was stirred at room temperature for 48 hr. The reaction mixture was diluted with diethyl ether (50 mL) and the organic layer was washed with aqueous solutions of ammonium chloride (50 mL), sodium bicarbonate (50 mL), and NaCl (50 mL), followed by drying over sodium sulfate. The organic layer was concentrated in vacuo, followed by preparative TLC using 15% methanol in dichloromethane as the mobile phase to yield the title compound (4.5 mg, 5.0%). 1H NMR (CDCl3, 300 MHz): δ 7.30 (d, 1H, J=11.6 Hz), 7.17-7.12 (br m, 2H), 7.04 (d, 2H, J=11.6 Hz), 6.78 (d, 2H, J=11.6 Hz), 4.52 (dt, 2H, J1=5.6 Hz, J2=63.6 Hz), 4.33 (br s, 1H), 4.13 (br s, 1H), 4.04-3.96 (m, 4H), 3.81-3.67 (m, 5H), 3.63-3.49 (m, 2H), 3.38-3.21 (m, 3H), 2.78 (br s, 1H), 1.77 (br s, 2H); LC/MS: theoretical mass=470.15; observed M+1=471.6, M+Na=493.4).

Workup

  1. additionwas added to a flask
  2. washthe organic layer was washed with aqueous solutions of ammonium chloride (50 mL), sodium bicarbonate (50 mL), and NaCl (50 mL)
  3. dry with materialby drying over sodium sulfate
  4. concentrationThe organic layer was concentrated in vacuo

Sources & evidence

ORD record
ord-dce722ce3c9e485e8524c460c4239c2a
Source dataset
uspto-grants-2012_01
Patent number
US08106021B2

Reaction notes

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