Chloroacetyl chloride → cis-1-(2-Chloroacetyl)-5-(4-methoxy-2,3-dimethylphenyl)pyrrolidine-2-carboxylic acid ethyl ester

HRID 851957Notes

Reaction equation

HRID 851957 reaction equation
[Cl:1][CH2:2][C:3](Cl)=[O:4].[CH2:6]([O:8][C:9]([C@H:11]1[CH2:15][CH2:14][C@@H:13]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([CH3:24])[C:17]=2[CH3:25])[NH:12]1)=[O:10])[CH3:7].CCN(CC)CC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH2:6]([O:8][C:9]([C@H:11]1[CH2:15][CH2:14][C@@H:13]([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([CH3:24])[C:17]=2[CH3:25])[N:12]1[C:3](=[O:4])[CH2:2][Cl:1])=[O:10])[CH3:7]

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 69367981HCID 69367981, compound

Product 1

HCID 69445732cis-1-(2-Chloroacetyl)-5-(4-methoxy-2,3-dimethylphenyl)pyrrolidine-2-carboxylic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Chloroacetyl chloride (1.7 mL, 21.5 mmol) To a solution of cis-5-(4-methoxy-2,3-dimethylphenyl)pyrrolidine-2-carboxylic acid ethyl ester (16.56 mmol) and Et3N (3.5 mL, 24.8 mmol) in CH2Cl2 (80 mL) at 0° C. The reaction mixture is stirred at 0° C. for 15 min and then at room temperature for 45 min. The mixture then poured into half-saturated aq. NaHCO3 (100 mL) and extracted with EtOAc. The extract is further washed with water (1×50 mL) and brine (1×50 mL). The aqueous washes are reextracted once with EtOAc, and the combined extracts are dried over Na2SO4, and concentrated. The crude material is used in the next step without further purification. 1H NMR (CDCl3, 400 MHz): 7.90 (d, J=8.6 Hz, 1H), 6.78 (d, J=8.6 Hz, 1H), 5.30 (dd, J=7.6, 3.6 Hz, 1H), 4.53 (t, J=8.0 Hz, 1H), 4.37-4.21 (m, 2H), 3.81 (s, 3H), 3.77, 3.65 (ABq, J=13.2 Hz, 2H), 2.50-2.41 (m, 1H), 2.26 (s, 3H), 2.24-2.14 (m, 1H), 2.19 (s, 3H), 2.09-2.00 (m, 1H), 1.96-1.89 (m, 1H), 1.35 (t, J=7.2 Hz, 3H). Electrospray MS: m/z 354 [M+1].

Workup

  1. customat 0° C
  2. waitat room temperature for 45 min
  3. extractionextracted with EtOAc
  4. washThe extract is further washed with water (1×50 mL) and brine (1×50 mL)
  5. dry with materialthe combined extracts are dried over Na2SO4
  6. concentrationconcentrated
  7. customThe crude material is used in the next step without further purification

Sources & evidence

ORD record
ord-f9e415eb8fe64a4ebad7f50a3bd68a63
Source dataset
uspto-grants-2007_08
Patent number
US07253168B2

Reaction notes

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