Methanol → 1-Benzyl 4-methyl piperidine-1,4-dicarboxylate

HRID 2180197Notes

Reaction equation

HRID 2180197 reaction equation
O=S(Cl)Cl.[CH2:5]([O:12][C:13]([N:15]1[CH2:20][CH2:19][CH:18]([C:21]([OH:23])=[O:22])[CH2:17][CH2:16]1)=[O:14])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH3:24]O>>[CH3:24][O:22][C:21]([CH:18]1[CH2:17][CH2:16][N:15]([C:13]([O:12][CH2:5][C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)=[O:14])[CH2:20][CH2:19]1)=[O:23]

Participants

4

Reactant 3

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 7364891-Carbobenzoxy-4-piperidinecarboxylic Acid

Product 1

HCID 15125441-Benzyl 4-methyl piperidine-1,4-dicarboxylateYield 82%

Procedure

SOCl2 (9.62 mL, 132 mmol, 2 eq.) was carefully added to cold MeOH (130 mL) at −30° C. followed by the addition of 1-benzyloxycarbonyl-piperidine-4-carboxylic acid (17.3 g, 66 mmol) in one portion. The mixture was stirred at room temperature for 3 h then was bubbled with N2 inside the hood and the resulting solution was concentrated by rotary evaporation. The residue was taken up into EtOAc (200 mL) and washed with saturated aqueous NaHCO3 (200 mL) and saturated brine (100 mL) and the organic extracts were dried over Na2SO4, filtered and concentrated by rotary evaporation to give 1-benzyloxycarbonyl-piperidine-4-carboxylic acid methyl ester as a colorless oil (15 g, 54 mmol, 82%). 1H NMR (300 MHz, CDCl3): δ 7.46 (m, 5H), 5.24 (s, 2H), 4.21 (m, 2H), 3.81 (s, 3H), 3.05 (t, 2H), 2.60 (m, 1H), 2.03 (m, 2H), 1.78 (m, 2H).

Workup

  1. customthen was bubbled with N2 inside the hood
  2. concentrationthe resulting solution was concentrated by rotary evaporation
  3. washwashed with saturated aqueous NaHCO3 (200 mL) and saturated brine (100 mL)
  4. dry with materialthe organic extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation

Sources & evidence

ORD record
ord-e752d7ae7b77449d95cfe210aa52aa0e
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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