1,2-Dichloroethane → (2S,4R)-methyl 1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-4-(2-chlorophenylsulfonyl)pyrrolidine-2-carboxylate

HRID 1025328Notes

Reaction equation

HRID 1025328 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]([OH:13])=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)CC)C.[Cl:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][C:37]=1[S:42]([C@H:45]1[CH2:49][NH:48][C@H:47]([C:50]([O:52][CH3:53])=[O:51])[CH2:46]1)(=[O:44])=[O:43].Cl>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([C:11]([N:48]3[CH2:49][C@H:45]([S:42]([C:37]4[CH:38]=[CH:39][CH:40]=[CH:41][C:36]=4[Cl:35])(=[O:44])=[O:43])[CH2:46][C@H:47]3[C:50]([O:52][CH3:53])=[O:51])=[O:13])[CH2:9][CH2:10]2)=[CH:6][CH:7]=1

Participants

8

Reactant 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 986061-(p-Chlorophenyl)cyclopropanecarboxylic acidHCID 66770749(2S,4R)-methyl 4-(2-chlorophenylsulfonyl)pyrrolidine-2-carboxylate

Product 1

HCID 86762435(2S,4R)-methyl 1-(1-(4-chlorophenyl)cyclopropanecarbonyl)-4-(2-chlorophenylsulfonyl)pyrrolidine-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under an atmosphere of argon, 1-(4-chlorophenyl)cyclopropanecarboxylic acid (1.57 g, 7.9 mmol, Eq: 1.20) was combined with tetrahydrofuran (70.0 ml) to give a colorless solution. Then EDC (3.09 g, 15.8 mmol, Eq: 2.40), HOBt (2.47 g, 15.8 mmol, Eq: 2.40) and triethylamine (6.66 g, 9.18 ml, 65.8 mmol, Eq: 10.0) was added. (A white suspension was obtained.) The reaction mixture was stirred for 15 min at room temperature. A solution of (2S,4R)-methyl 4-(2-chlorophenylsulfonyl)pyrrolidine-2-carboxylate (2 g, 6.58 mmol, Eq: 1.00) in tetrahydrofuran (14.0 ml) was added dropwise. The reaction was stirred for 3 days at room temperature. The reaction mixture was poured into 75 ml HCl 1M and extracted with 2×100 ml ethyl acetate. The organic layers were washed with 75 ml satd. Na2CO3 solution and 75 ml brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (50 g column, from 0% to 100% ethyl acetate in heptane). The title compound was obtained as a light yellow solid (1.5 g, 47.2%, MS (m/e)=482.3 [M+H+]).

Workup

  1. customto give a colorless solution
  2. custom(A white suspension was obtained
  3. stirringThe reaction was stirred for 3 days at room temperature
  4. extractionextracted with 2×100 ml ethyl acetate
  5. washThe organic layers were washed with 75 ml
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by flash chromatography (50 g column, from 0% to 100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-9ed6f614e4a44241a3f4652ed5382665
Source dataset
uspto-grants-2014_05
Patent number
US08729061B2

Reaction notes

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