Pyrrolidine → α-3-Thienyl-1-pyrrolidineacetic acid

HRID 874735Notes

Reaction equation

HRID 874735 reaction equation
O.[C:2]([OH:6])(=[O:5])[CH:3]=O.[NH:7]1[CH2:11][CH2:10][CH2:9][CH2:8]1.[S:12]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13]1>C(Cl)Cl>[N:7]1([CH:3]([C:14]2[CH:15]=[CH:16][S:12][CH:13]=2)[C:2]([OH:6])=[O:5])[CH2:11][CH2:10][CH2:9][CH2:8]1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 581760Thiophene-3-boronic acidHCID 15620607Glyoxylic acid, monohydrate

Product 1

HCID 43803511α-3-Thienyl-1-pyrrolidineacetic acidYield 93.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of glyoxylic acid monohydrate (10.79 g, 0.11 mol) and pyrrolidine (9.69 mL, 0.11 mol) in DCM (375 mL) was sonicated for 15 minutes. Thiophene-3-boronic acid (15 g, 0.11 mol) was added and the mixture was stirred at rt for 24 h. The solid was filtered and washed with little DCM to gave 38 g crude product as crop-1. The mother liquor concentrated under reduced pressure to give an additional 4 g as crop-2. The combined crude product purified by Biotgae SNAP 100 g silica column (gradient 0-50% MeOH in DCM) gave the title compound as a cream solid (21.7 g, 70%). 1H NMR (400 MHz, CD3OD) δ ppm 7.66 (dd, J=2.8 Hz, J=1.2 Hz, 1H), 7.53 (dd, J=5.2 Hz, J=2.8 Hz, 1H), 7.28 (dd, J=5.2 Hz, J=1.2 Hz, 1H), 4.65 (s, 1H), 3.06 (br. s, 2H), 2.04-1.95 (br. s, 4H), 2H merged with solvent peak; MS ESI 212 [M+H]+, calcd for [C10H13NO2S+H]+ 212.07.

Workup

  1. customwas sonicated for 15 minutes
  2. filtrationThe solid was filtered
  3. washwashed with little DCM
  4. customto gave 38 g crude product as crop-1
  5. concentrationThe mother liquor concentrated under reduced pressure
  6. customto give an additional 4 g as crop-2
  7. custompurified by Biotgae SNAP 100 g silica column (gradient 0-50% MeOH in DCM)

Sources & evidence

ORD record
ord-fc5c063762354e74b481af7eed096378
Source dataset
uspto-grants-2015_03
Patent number
US08980934B2

Reaction notes

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