Dimethylformamide → (RS)-4-[1-(4-m-tolyl-butyl)-pyrrolidine-3-sulfonyl]-phenol

HRID 1280719Notes

Reaction equation

HRID 1280719 reaction equation
[CH2:1]([N:5]1[CH2:9][CH2:8][CH:7]([S:10]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)(=[O:12])=[O:11])[CH2:6]1)[CH2:2][CH:3]=[CH2:4].CN(C=O)C.Br[C:26]1[CH:27]=[C:28]([CH3:32])[CH:29]=[CH:30][CH:31]=1.C([O-])([O-])=O.[K+].[K+]>C1COCC1.B1C2CCCC1CCC2>[C:28]1([CH3:32])[CH:29]=[CH:30][CH:31]=[C:26]([CH2:4][CH2:3][CH2:2][CH2:1][N:5]2[CH2:9][CH2:8][CH:7]([S:10]([C:13]3[CH:14]=[CH:15][C:16]([OH:19])=[CH:17][CH:18]=3)(=[O:12])=[O:11])[CH2:6]2)[CH:27]=1

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 115603-BromotolueneHCID 18425811(RS)-4-(1-but-3-enyl-pyrrolidine-3-sulfonyl)-phenol

Product 1

HCID 10292749(RS)-4-[1-(4-m-tolyl-butyl)-pyrrolidine-3-sulfonyl]-phenolYield 47%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 789669-Borabicyclo(3.3.1)nonaneSolvent

Procedure

To a 0° C. solution of (RS)-4-(1-but-3-enyl-pyrrolidine-3-sulfonyl)-phenol (0.106 g, 0.378 mmol) in THF (0.5 ml), 9-BBN (1.66 ml, 0.74 ml, 0.5 M solution in THF) was added dropwise. The reaction mixture was allowed to warm up slowly to room temperature. After 4 hours stirring, the reaction mixture was treated successively with DMF (1.5 ml), 3-bromotoluene (0.046 ml, 0.377 mmol), PdCl2(dppf)2-dichloromethane complex (9.3 mg, 0.01 mmol), and K2CO3 (95 mg, 0.69 mmol). After 5 hours stirring at 60° C., the reaction mixture was cooled to room temperature, quenched with ethylacetate and H2O. The aqueous phase was extracted with ethylacetate. The combined organic phases were washed with H2O, dried over Na2SO4, filtered and concentrated. The residue was chromatographed over silica gel (CH2Cl2—MeOH, 98:2) to provide (RS)-4-[1-(4-m-tolyl-butyl)-pyrrolidine-3-sulfonyl]-phenol (66 mg, 47%) as a light yellow foam, MS: m/e=374.4 (M+H+).

Workup

  1. stirringAfter 5 hours stirring at 60° C.
  2. temperaturethe reaction mixture was cooled to room temperature
  3. customquenched with ethylacetate and H2O
  4. extractionThe aqueous phase was extracted with ethylacetate
  5. washThe combined organic phases were washed with H2O
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was chromatographed over silica gel (CH2Cl2—MeOH, 98:2)

Sources & evidence

ORD record
ord-f269abf6f5f34efb841c1c5ecdf5fab0
Source dataset
uspto-grants-2002_09
Patent number
US06451819B2

Reaction notes

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