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

HRID 489147Notes

Reaction equation

HRID 489147 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)C>CO>[CH3:13][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]

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 69020300[(Z)-4-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]acetic acid methyl esterYield 64.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

p-Toluenesulfonic acid hydrate (620 mg, 3.26 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 (1.10 g, 3.08 mmol) in MeOH (10 mL). After 17 h at rt, the reaction was quenched with saturated aqueous NaHCO3 (20 mL) and the mixture was extracted with CH2Cl2 (3×30 mL). The combined organic phase was dried (Na2SO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (40% EtOAc/CH2Cl2→60% EtOAc/CH2Cl2, gradient, then 7% MeOH/CH2Cl2) afforded 538 mg (64%) of [(Z)-4((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-but-2-enyloxy]-acetic acid methyl ester.

Workup

  1. customthe reaction was quenched with saturated aqueous NaHCO3 (20 mL)
  2. extractionthe mixture was extracted with CH2Cl2 (3×30 mL)
  3. dry with materialThe combined organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customPurification of the residue by flash column chromatography on silica gel (40% EtOAc/CH2Cl2→60% EtOAc/CH2Cl2, gradient

Sources & evidence

ORD record
ord-ef004080dd004f6b8ed9b83fa4faa4ee
Source dataset
uspto-grants-2005_12
Patent number
US06977260B2

Reaction notes

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