Cesium carbonate → HCID 86635435, compound

HRID 599484Notes

Reaction equation

HRID 599484 reaction equation
[CH3:1][O:2][C:3]([C:5]1[N:6]([CH3:23])[C:7]([S:10]([N:13]2[CH2:17][CH2:16][C@H:15](OS(C)(=O)=O)[CH2:14]2)(=[O:12])=[O:11])=[CH:8][CH:9]=1)=[O:4].C(=O)([O-])[O-].[Cs+].[Cs+].[C:30]([C:34]1[CH:39]=[C:38]([SH:40])[CH:37]=[C:36]([C:41]([CH3:44])([CH3:43])[CH3:42])[C:35]=1[OH:45])([CH3:33])([CH3:32])[CH3:31]>CCC(C)=O.O.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[N:6]([CH3:23])[C:7]([S:10]([N:13]2[CH2:17][CH2:16][C@@H:15]([S:40][C:38]3[CH:37]=[C:36]([C:41]([CH3:42])([CH3:43])[CH3:44])[C:35]([OH:45])=[C:34]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH:39]=3)[CH2:14]2)(=[O:11])=[O:12])=[CH:8][CH:9]=1)=[O:4]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 703702,6-Di-tert-butyl-4-mercaptophenolHCID 86635434HCID 86635434, compound

Product 1

HCID 86635435HCID 86635435, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6569Methyl Ethyl KetoneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (S)-5-(3-methanesulfonyloxy-pyrrolidine-1-sulfonyl)-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester (Ex. 13b, 7.75 g, 21.2 mmol) and cesium carbonate (11.6 g, 31.8 mmol) in degassed MEK (85 mL) at 60° C. was added 2,6-di-tert-butyl-4-mercaptophenol (7.6 g, 31.8 mmol). The resulting solution was stirred at 60° C. for 3 h. Upon completion, as determined by HPLC, the reaction was diluted with H2O (200 mL) and Ethyl acetate (100 mL). The layers were cut and the aqueous layer was extracted with Ethyl acetate (3×100 mL). The combined organic cuts were washed with a saturated ammonium chloride solution (1×100 mL), a 50% aqueous brine solution (1×100 mL) and brine (1×100 mL), dried over Na2SO4, and concentrated under reduced pressure. Silica gel chromatography (Ethyl acetate:hexanes, 1:2) afforded 9.34 g (87%) of (R)-5-[3-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-pyrrolidine-1-sulfonyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester as a white solid, mp 83-85° C. 1H-NMR (400 MHz, CDCl3): δ 7.23 (d, 1H, J=2.0 Hz), 7.21 (s, 2H), 7.17 (d, 1H, J=2.0 Hz), 5.30 (s, 1H), 3.97 (s, 3H), 3.84 (s, 3H), 3.59 (dd, 1H, J=10.4, 7.2 Hz), 3.47 (pentet, 1H, J=6.8 Hz), 3.28-3.39 (m, 2H), 3.10 (dd, 1H, J=10.4, 6.4 Hz), 2.12-2.20 (m, 1H), 1.75-1.84 (m, 1H), 1.42 (s, 18H). Anal. Calcd. for C25H36N2O5S2: C, 59.03; H, 7.13; N, 5.51; S, 12.61. Found: C, 59.63; H, 7.34; N, 5.39; S, 12.23.

Workup

  1. extractionthe aqueous layer was extracted with Ethyl acetate (3×100 mL)
  2. washThe combined organic cuts were washed with a saturated ammonium chloride solution (1×100 mL)
  3. dry with materiala 50% aqueous brine solution (1×100 mL) and brine (1×100 mL), dried over Na2SO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1bf5752cd72e4ce6b128be65e73d0ca6
Source dataset
uspto-grants-2011_03
Patent number
US07897776B2

Reaction notes

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