Water → 3,5-Dichloro-4-((1-(cis-2-methylcyclohexyl)-2-oxopyrrolidin-3-yl)methyl)phenyl trifluoromethanesulfonate

HRID 2235223Notes

Reaction equation

HRID 2235223 reaction equation
[Cl:1][C:2]1[CH:21]=[C:20]([OH:22])[CH:19]=[C:18]([Cl:23])[C:3]=1[CH2:4][CH:5]1[CH2:9][CH2:8][N:7]([C@@H:10]2[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:11]2[CH3:16])[C:6]1=[O:17].CCN(CC)CC.[O:31](S(C(F)(F)F)(=O)=O)[S:32]([C:35]([F:38])([F:37])[F:36])(=O)=[O:33].O>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:36][C:35]([F:38])([F:37])[S:32]([O:22][C:20]1[CH:19]=[C:18]([Cl:23])[C:3]([CH2:4][CH:5]2[CH2:9][CH2:8][N:7]([C@@H:10]3[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:11]3[CH3:16])[C:6]2=[O:17])=[C:2]([Cl:1])[CH:21]=1)(=[O:33])=[O:31]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 67749Trifluoromethanesulfonic anhydrideHCID 684690153-(2,6-Dichloro-4-hydroxybenzyl)-1-(cis-2-methylcyclohexyl)pyrrolidin-2-one

Product 1

HCID 874637973,5-Dichloro-4-((1-(cis-2-methylcyclohexyl)-2-oxopyrrolidin-3-yl)methyl)phenyl trifluoromethanesulfonateYield 88%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Dissolve 3-(2,6-dichloro-4-hydroxybenzyl)-1-(cis-2-methylcyclohexyl)pyrrolidin-2-one (1.0 g, 2.81 mmol) in DCM (100 mL) and cool to 0° C. under N2. Add DMAP (0.069 g, 0.56 mmol), Et3N (2.84 g, 28.01 mmol), and Tf2O (0.83 g, 2.95 mmol) at the same temperature. Stir the reaction for six hour and then add water (100 mL). Extract the aqueous layer with dichloromethane (3×100 mL). Combine the organic layers and dry with Na2SO4, filter, concentrate and purify by flash column chromatography (silica gel, 20-50% of EtOAc-Hexane) to give 1.2 g (88%) of the title compound as a colorless oil. 1H NMR (CDCl3) δ 7.28 (s, 2H), 4.02 (m, 1H), 3.46 (m, 2H), 3.38 (m, 1H), 3.02 (m, 1H), 2.91 (m, 1H), 2.35 (m, 1H), 2.02 (m, 1H), 1.31-1.87 (m, 9H), 0.92 (d, 3H).

Workup

  1. customthe reaction for six hour
  2. extractionExtract the aqueous layer with dichloromethane (3×100 mL)
  3. dry with materialCombine the organic layers and dry with Na2SO4
  4. filtrationfilter
  5. concentrationconcentrate
  6. custompurify by flash column chromatography (silica gel, 20-50% of EtOAc-Hexane)

Sources & evidence

ORD record
ord-da55ee9629e44efbb9b393949da853d7
Source dataset
uspto-grants-2010_05
Patent number
US07713979B2

Reaction notes

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