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

HRID 349355Notes

Reaction equation

HRID 349355 reaction equation
O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH3:13][O:14][C:15](=[O:36])[CH2:16][O:17][CH2:18][C:19]#[C:20][CH2:21][N:22]1[C:27](=[O:28])[CH2:26][CH2:25][CH2:24][C@@H:23]1[CH2:29][O:30]C(OCC)C>CO>[CH3:13][O:14][C:15](=[O:36])[CH2:16][O:17][CH2:18][C:19]#[C:20][CH2:21][N:22]1[C:27](=[O:28])[CH2:26][CH2:25][CH2:24][C@@H:23]1[CH2:29][OH:30]

Participants

4

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 69021961(4-[(R)-2-(1-ethoxy-ethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester

Product 1

HCID 69021580[4-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-but-2-ynyloxy]-acetic acid methyl esterYield 26%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

p-Toluenesulfonic acid hydrate (289 mg, 1.52 mmol) was added to a solution of {4-[(R)-2-(1-ethoxy-ethoxymethyl)-6-oxo-piperidin-1-yl]-but-2-ynyloxy}-acetic acid methyl ester (494 mg, 1.45 mmol) in MeOH (5.0 mL) at rt. After 20 h at rt, the mixture was concentrated in vacuo, treated with saturated aqueous NaHCO3 (20 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic phase was dried (MgSO4), filtered and concentrated in vacuo. Purification of the residue by flash column chromatography on silica gel (CH2Cl2→3% MeOH/CH2Cl2, gradient) afforded 100 mg (26%) of [4-((R)-2-hydroxymethyl-6-oxo-piperidin-1-yl)-but-2-ynyloxy]-acetic acid methyl ester.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. additiontreated with saturated aqueous NaHCO3 (20 mL)
  3. extractionextracted with CH2Cl2 (3×20 mL)
  4. dry with materialThe combined organic phase was dried (MgSO4)
  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-337dbe930ade4241a58336a3b3114548
Source dataset
uspto-grants-2007_02
Patent number
US07179820B2

Reaction notes

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