Methyl bromoacetate → HCID 57894613, compound

HRID 1822182Notes

Reaction equation

HRID 1822182 reaction equation
C(N(CC)C(C)C)(C)C.Br[CH2:11][C:12]([O:14][CH3:15])=[O:13].[CH2:16]([NH:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[C:26]([Cl:31])[CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C.CCOC(C)=O>[CH2:16]([N:23]([C:24]1[CH:29]=[CH:28][C:27]([F:30])=[C:26]([Cl:31])[CH:25]=1)[CH2:11][C:12]([O:14][CH3:15])=[O:13])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 3

HCID 60984Methyl bromoacetate2×HCID 81531DiisopropylethylamineHCID 961624HCID 961624, compound

Product 1

HCID 57894613HCID 57894613, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

N,N-Diisopropylethylamine (1.47 mL, 8.45 mmol) and then methyl bromoacetate (1.29 g, 8.45 mmol) were added to a solution of N-benzyl-3-chloro-4-fluoroaniline (7-1, 1.00 g, 4.23 mmol) in DMF (7 mL), and the resulting mixture was stirred at 50° C. for 2 h, 60° C. for 3 h, and then 50° C. for 18 h. Methyl bromoacetate (0.4 mL, 4 mmol) was added and mixture was heated to 60° C. for 7 h and then 50° C. for 18 h. The reaction was diluted with EtOAc (100 mL) and washed with saturated aqueous ammonium chloride (3×100 mL), H2O (100 mL), and brine (50 mL). The reaction was concentrated and purified residue by flash column chromatography (SiO2, 0-20% EtOAc/hexanes gradient) to provide methyl N-benzyl-N-(3-chloro-4-fluorophenyl)glycinate (7-2). 1H NMR (300 MHz, CDCl3) δ 7.38-7.25 (m, 5H), 6.97 (dd, J=8.9, 8.9 Hz, 1H), 6.69 (dd, J=6.1, 3.1 Hz, 1H), 6.50 (ddd, J=8.9, 3.4, 3.4 Hz, 1H), 4.59 (s, 2H), 4.05 (s, 2H), 3.76 (s, 3H).

Workup

  1. wait50° C. for 18 h
  2. temperaturemixture was heated to 60° C. for 7 h
  3. wait50° C. for 18 h
  4. washwashed with saturated aqueous ammonium chloride (3×100 mL), H2O (100 mL), and brine (50 mL)
  5. concentrationThe reaction was concentrated
  6. custompurified residue by flash column chromatography (SiO2, 0-20% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-802ad56498014ac5858222f9fc7d4de2
Source dataset
uspto-grants-2009_10
Patent number
US07608739B2

Reaction notes

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