4-Methylmorpholine → ethyl 2-[3-(2-fluorophenyl)-N-methylprop-2-ynoylamino]acetate

HRID 1837947Notes

Reaction equation

HRID 1837947 reaction equation
Cl.[CH2:2]([O:4][C:5](=[O:9])[CH2:6][NH:7][CH3:8])[CH3:3].[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]#[C:18][C:19]([OH:21])=O.CN1CCOCC1.CCN=C=NCCCN(C)C.Cl>CN(C1C=CN=CC=1)C.C(Cl)Cl>[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]#[C:18][C:19]([N:7]([CH2:6][C:5]([O:4][CH2:2][CH3:3])=[O:9])[CH3:8])=[O:21]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 171173Ethyl N-methylaminoacetate hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 226776553-(2-Fluorophenyl)prop-2-ynoic acid

Product 1

HCID 22677637ethyl 2-[3-(2-fluorophenyl)-N-methylprop-2-ynoylamino]acetateYield 77%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of sarcosine ethyl ester hydrochloride (1.14 g, 7.44 mmol) and 3-(2-fluorophenyl)prop-2-ynoic acid (1.22 g, 7.44 mmol) in anhyd. CH2Cl2 was added NMM (10 mL, 8.93 mmol), followed by EDCI.HCl (1.86 g, 9.67 mmol) and DMAP (0.99 g, 8.2 mmol). The reaction mixture was stirred for 5 h at room temperature and diluted with CH2Cl2. The resulting solution was washed with a 0.5N HCl solution (2×25 mL), a 0.5N NaOH solution (2×25 mL) and a saturated NaCl solution. The organic layer was dried (MgSO4), concentrated onto silica gel under reduced pressure and purified by flash chromatography (30% EtOAc/hex) to yield ethyl 2-[3-(2-fluorophenyl)-N-methylprop-2-ynoylamino]acetate (1.50 g, 77%) as a yellow oil: TLC (50% EtOAc/hex) Rf 0.54; HPLC ES-MS m/z (rel abundance) 264 (100%).

Workup

  1. washThe resulting solution was washed with a 0.5N HCl solution (2×25 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. concentrationconcentrated onto silica gel under reduced pressure
  4. custompurified by flash chromatography (30% EtOAc/hex)

Sources & evidence

ORD record
ord-a3da3d9170fe4122b993daad3592f5b9
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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