Cesium carbonate → HCID 66704686, compound

HRID 2403710Notes

Reaction equation

HRID 2403710 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH: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.CS(O[CH2:32][CH2:33][O:34][CH2:35][CH2:36][NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>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][CH2:32][CH2:33][O:34][CH2:35][CH2:36][NH:37][C:38](=[O:39])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 12106196tert-butyl N-{2-[2-(methanesulfonyloxy)ethoxy]ethyl}carbamateHCID 57809578HCID 57809578, compound2×

Product 1

HCID 66704686HCID 66704686, compoundYield 0.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(3R,4R,5S,6R)-2-(4-chloro-3-(4-hydroxybenzyl)phenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol (intermediate D) (30 mg, 78.7 mmol), 2-(2-(tert-butoxycarbonylamino)ethoxy)ethyl methanesulfonate (26.8 mg, 94.5 mmol) and Cs2CO3 (30.8 mg, 94.5 mmol) were dissolved in DMF (3 ml) at room temperature and stirred overnight. The mixture was then extracted with EtOAc, washed with NH4Cl and NaCl, dried over Na2SO4, and evaporated to get the crude product, tert-butyl 2-(2-(4-(2-chloro-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl)benzyl)phenoxy)ethoxy)ethylcarbamate (intermediate U) (40 mg), which was used for the next step without further purification. The crude intermediate U was dissolved in MeOH (0.5 mL), MeSO3H (6 μL) was added, and the mixture was stirred overnight at room temperature. Then the reaction was quenched with NaHCO3, the mixture was extracted with ethyl acetate, and the organic layer was washed with brine, dried over Na2SO4, concentrated, and separated by preparative HPLC to obtain compound V (11.6 mg). 1H NMR (CD3OD): δ 7.40˜7.27 (m, 3H), 7.14˜7.10 (m, 2H), 6.87˜6.85 (m, 2H), 4.54 (d, J=16, 1H), 4.19˜4.18 (m, 1H), 4.16˜4.14 (m, 2H), 4.05˜4.01 (m, 4H), 3.94˜3.93 (m, 1H), 3.88˜3.86 (m, 2H), 3.83˜3.76 (m, 3H), 3.67˜3.57 (m, 1H), 3.16˜3.13 (m, 2H); MS ESI (m/z): 468 (M+H)+, calc. 467.

Workup

  1. extractionThe mixture was then extracted with EtOAc
  2. washwashed with NH4Cl and NaCl
  3. dry with materialdried over Na2SO4
  4. customevaporated

Sources & evidence

ORD record
ord-0c20defb7cb74e46b918410bd8404822
Source dataset
uspto-grants-2014_08
Patent number
US08802637B2

Reaction notes

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