Cesium carbonate → HCID 25197072, compound

HRID 2038510Notes

Reaction equation

HRID 2038510 reaction equation
CC1C=CC(S(O[CH2:12][CH2:13][O:14][CH2:15][CH:16]([F:18])[F:17])(=O)=O)=CC=1.[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([C@H:26]2[C@H:31]([OH:32])[C@@H:30]([OH:33])[C@H:29]([OH:34])[C@@H:28]([CH2:35][OH:36])[O:27]2)=[CH:22][C:21]=1[CH2:37][C:38]1[CH:43]=[CH:42][C:41]([OH:44])=[CH:40][CH:39]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.C(OCC)C>[Cl:19][C:20]1[CH:25]=[CH:24][C:23]([C@H:26]2[C@H:31]([OH:32])[C@@H:30]([OH:33])[C@H:29]([OH:34])[C@@H:28]([CH2:35][OH:36])[O:27]2)=[CH:22][C:21]=1[CH2:37][C:38]1[CH:39]=[CH:40][C:41]([O:44][CH2:12][CH2:13][O:14][CH2:15][CH:16]([F:18])[F:17])=[CH:42][CH:43]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 44580555Bms-5119262×HCID 59557759HCID 59557759, compound

Product 1

HCID 25197072HCID 25197072, compoundYield 6.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

2-(2,2-difluoroethoxy)ethyl 4-methylbenzenesulfonate (53 mg, 0.19 mmol) dissolved in anhydrous DMF (3 mL) was added to a reaction 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 (98 mg, 0.30 mmol) was added to the flask, and the resulting mixture was stirred for 48 hr at room temperature. The reaction was diluted with diethyl ether (50 mL) and the organic layer was washed with an aqueous solution of ammonium chloride (50 mL), sodium bicarbonate (50 mL), and NaCl (50 ml), after which it was dried over sodium sulfate, filtered and concentrated en vacuo. The residue was purified by preparative TLC using 15% methanol in dichloromethane as the mobile phase to yield the title compound (4.6 mg, 5.0%). 1H NMR (CDCl3, 300 MHz): δ 7.33 (d, 1H, J=11.2 Hz), 7.15 (d, 1H, J=11.2 Hz), 7.14 (s, 1H), 7.06 (d, 2H, J=11.6 Hz), 6.79 (d, 2H, J=11.6 Hz), 5.86 (tt, 1H, J1=5.2 Hz, J2=66.4 Hz), 4.07-3.98 (m, 3H), 3.87-3.84 (m, 3H), 3.84-3.71 (m, 2H), 3.74 (td, 2H, J1=5.6 Hz, J2=18.4 Hz), 3.66-3.54 (m, 3H), 3.30-3.36 (m, 2H), 2.78 (br s, 1H), 2.42 (br s, 1H), 1.65 (s, 2H); LC/MS: theoretical mass=488.14; observed M+1=489.2, M+Na=511.4).

Workup

  1. additionwas added to a reaction flask
  2. washthe organic layer was washed with an aqueous solution of ammonium chloride (50 mL), sodium bicarbonate (50 mL), and NaCl (50 ml)
  3. dry with materialafter which it was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated en vacuo
  6. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-682f8200e4714c91b666629ba7db617c
Source dataset
uspto-grants-2013_11
Patent number
US08575321B2

Reaction notes

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