Cesium carbonate → HCID 66704686, compound

HRID 2038466Notes

Reaction equation

HRID 2038466 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-9856a7c3b92e4a7a9d14e8c0694fd2f6
Source dataset
uspto-grants-2013_11
Patent number
US08575321B2

Reaction notes

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