Tert-butyl 2-(2-chloroacetamido)acetate → 2-{2-[(2E)-3-(Methoxycarbonyl)prop-2-enoyloxy]acetylamino}acetic acid

HRID 1624168

Reaction equation

HRID 1624168 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].Cl[CH2:11][C:12]([NH:14][CH2:15][C:16]([O:18]C(C)(C)C)=[O:17])=[O:13].C(=O)([O-])O.[Cs+]>CN1C(=O)CCC1>[CH3:9][O:8][C:1](/[CH:2]=[CH:3]/[C:4]([O:6][CH2:11][C:12]([NH:14][CH2:15][C:16]([OH:18])=[O:17])=[O:13])=[O:5])=[O:7]

Participants

5

Reactant 3

HCID 262730Tert-butyl 2-(2-chloroacetamido)acetateHCID 2734983Cesium bicarbonateHCID 5369209Monomethyl Fumarate

Product 1

HCID 461791542-{2-[(2E)-3-(Methoxycarbonyl)prop-2-enoyloxy]acetylamino}acetic acidYield 12.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Following general procedure A, methyl hydrogen fumarate (MHF) (0.68 g, 5.26 mmol) dissolved in NMP was reacted at ca. 55° C. with tert-butyl 2-(2-chloroacetylamino)acetate (0.91 g, 4.38 mmol) in the presence of CsHCO3 (1.19 g, 6.13 mmol) of the tert-butyl-protected intermediate and then purified by silica gel column chromatography (Biotage) using a mixture of ethyl acetate (EtOAc) and hexanes (1:2 to 2:3 to 1:1) as eluent. The purified product was treated with 50% trifluoroacetic acid (TFA) in dichloromethane (DCM). Removal of solvents afforded 0.13 g (12% yield) of the title compound (6). 1H NMR (CD3OD, 400 MHz): δ 6.96-6.93 (m, 2H), 4.74 (s, 2H), 3.98-3.95 (m, 2H), 3.81 (s, 3H). MS (ESI): m/z 246.00 (M+H)+, 244.02 (M−H)−.

Workup

  1. custompurified by silica gel column chromatography (Biotage)
  2. additiona mixture of ethyl acetate (EtOAc) and hexanes (1:2 to 2:3 to 1:1) as eluent
  3. additionThe purified product was treated with 50% trifluoroacetic acid (TFA) in dichloromethane (DCM)
  4. customRemoval of solvents

Sources & evidence

ORD record
ord-5b99c33d194d41aaafac6d71c4b21813
Source dataset
uspto-grants-2014_07
Patent number
US08778991B2

Linked notes

Loading…