p-Toluenesulfonic acid monohydrate → [(Z)-4-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]-acetic acid ethyl ester

HRID 489160Notes

Reaction equation

HRID 489160 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:13]([O:15][C:16](=[O:37])[CH2:17][O:18][CH2:19]/[CH:20]=[CH:21]\[CH2:22][N:23]1[C:28](=[O:29])[CH2:27][CH2:26][CH2:25][C@@H:24]1[CH2:30][O:31]C(OCC)C)[CH3:14]>CCO>[CH2:13]([O:15][C:16](=[O:37])[CH2:17][O:18][CH2:19]/[CH:20]=[CH:21]\[CH2:22][N:23]1[C:28](=[O:29])[CH2:27][CH2:26][CH2:25][C@@H:24]1[CH2:30][OH:31])[CH3:14]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 69022257{(Z)-4-[(R)-2-(1-ethoxyethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-enyloxy}-acetic acid ethyl ester

Product 1

HCID 69025613[(Z)-4-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]-acetic acid ethyl esterYield 76.4%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

p-Toluenesulfonic acid hydrate (267 mg, 1.40 mmol) was added to a solution of {(Z)-4-[(R)-2-(1-ethoxyethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-enyloxy}-acetic acid ethyl ester (from example 1, step 2, 477 mg, 1.33 mmol) in EtOH (6 mL). After 18 h at rt, the reaction was concentrated in vacuo and quenched with saturated aqueous NaHCO3 (20 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2 →3% MeOH/CH2Cl2, gradient) afforded 290 mg (76%) of [(Z)-4((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]-acetic acid ethyl ester.

Workup

  1. concentrationthe reaction was concentrated in vacuo
  2. customquenched with saturated aqueous NaHCO3 (20 mL)
  3. extractionThe mixture was extracted with CH2Cl2 (3×15 mL)
  4. dry with materialThe combined organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by flash column chromatography on silica gel (CH2Cl2 →3% MeOH/CH2Cl2, gradient)

Sources & evidence

ORD record
ord-aa6363fc4edf4b1c968d70424e13f4ef
Source dataset
uspto-grants-2005_12
Patent number
US06977260B2

Reaction notes

Loading…