Dimethylformamide → ((4-Chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-acetic acid methyl ester

HRID 408599Notes

Reaction equation

HRID 408599 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([N:12]2[CH2:15][CH2:14][C:13]2([CH3:19])[C:16]([OH:18])=O)=[O:11])[CH:5]=[C:6]([CH3:8])[CH:7]=1.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[CH3:31][O:32][C:33](=[O:44])[CH2:34][NH:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:31][O:32][C:33](=[O:44])[CH2:34][N:35]([CH2:36][C:37]1[CH:38]=[CH:39][C:40]([Cl:43])=[CH:41][CH:42]=1)[C:16]([C:13]1([CH3:19])[CH2:14][CH2:15][N:12]1[C:10](=[O:11])[CH2:9][C:4]1[CH:5]=[C:6]([CH3:8])[CH:7]=[C:2]([CH3:1])[CH:3]=1)=[O:18]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 19082816Methyl 2-{[(4-chlorophenyl)methyl]amino}acetateHCID 705580721-[2-(3,5-Dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid

Product 1

HCID 70558785((4-Chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

To a solution of 1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carboxylic acid, Intermediate 119 (1 eq.) in DCM under nitrogen, was added DMF (0.01 eq.) then oxalyl chloride (2 eq.). The solution was stirred at 20° C. for 30 min, then cooled to 0° C. A solution of (4-Chloro-benzylamino)-acetic acid methyl ester (1.5 eq.) and either TEA or DIPEA (2 to 7 eq.) in DCM was then added to the previous mixture. The solution was stirred at 0° C. for 1 h then at 20° C. until completion (1 h). The reaction was quenched with a saturated aqueous solution of NaHCO3 and extracted three times with DCM. The organic layers were combined, dried over MgSO4, filtered and concentrated under reduced pressure. The crude was purified by chromatography on silica gel (elution with heptane/EtOAc: 1/0 to 1/1) to afford ((4-chloro-benzyl)-{1-[2-(3,5-dimethyl-phenyl)-acetyl]-2-methyl-azetidine-2-carbonyl}-amino)-acetic acid methyl ester.

Workup

  1. temperaturecooled to 0° C
  2. stirringThe solution was stirred at 0° C. for 1 h
  3. customat 20° C.
  4. customuntil completion (1 h)
  5. customThe reaction was quenched with a saturated aqueous solution of NaHCO3
  6. extractionextracted three times with DCM
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude was purified by chromatography on silica gel (elution with heptane/EtOAc: 1/0 to 1/1)

Sources & evidence

ORD record
ord-da923f3d03fc4c6e99898eef570386b9
Source dataset
uspto-grants-2014_06
Patent number
US08759334B2

Reaction notes

Loading…