1,2-Dichloroethane → HCID 69585353, compound

HRID 2215968Notes

Reaction equation

HRID 2215968 reaction equation
[NH2:1][C:2]1[CH:6]([O:7][CH2:8][CH3:9])[O:5][C:4](=[O:10])[CH:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C@H:19]1[C:23]([OH:25])=[O:24])=[O:17])([CH3:14])([CH3:13])[CH3:12].C([BH3-])#N.[Na+].Cl.C(N(C(C)C)CC)(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>C(O)C.O1CCOCC1.C(OCC)(=O)C>[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C@@H:19]1[C:23](=[O:24])[NH:1][C@H:2]1[CH2:3][C:4](=[O:10])[O:5][C@H:6]1[O:7][CH2:8][CH3:9])=[O:17])([CH3:14])([CH3:13])[CH3:12].[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH2:20][C@@H:19]1[C:23](=[O:25])[NH:1][C@H:2]1[CH2:3][C:4](=[O:10])[O:5][C@@H:6]1[O:7][CH2:8][CH3:9])=[O:17])([CH3:12])([CH3:13])[CH3:14]

Participants

12

Reactant 7

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 5003444Sodium cyanoborohydrideHCID 219532364-amino-5-ethoxy-5H-furan-2-one

Product 2

HCID 69585204HCID 69585204, compoundHCID 69585353HCID 69585353, compoundYield 46.7%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4-amino-5-ethoxy-5H-furan-2-one (0.13 g, 0.75 mmol), (S)-pyrrolidine-1,2-dicarboxylic acid-1-tert-butyl ester (0.16 g, 0.75 mmol) and several crystals of Congo Red indicator in ethanol (5 mL) was treated with sodium cyanoborohydride (0.06 g, 0.90 mmol), followed by dropwise addition of 4M HCl in dioxane to attain and maintain a blueish color (˜pH3). The reaction was stirred 2 h, was filtered (Celite) and was evaporated. The residue was dissolved in dichloromethane (5 mL), was treated with di-isopropylethylamine (0.52 mL, 3.0 mmol), EDC (0.18 g, 0.94 mmol), and HOBT (0.13 g, 0.94 mmol) and was stirred at room temperature under nitrogen for 20 h. The reaction was diluted with ethyl acetate, was washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine, was dried over sodium sulfate, and was evaporated. Purification by flash chromatography (SiO2) eluted with 1:1 ethyl acetate:hexanes provided a 4:1 mixture (by 1H-NMR) of (R)-2-[(2R,3S)-2-ethoxy-5-oxo-tetrahydrofuran -3-ylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester and (R)-2-[(2S,3S)-2-ethoxy-5-oxo-tetrahydrofuran-3-ylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (0.06 g, 23% yield) as a colorless oil. 1H-NMR (500 MHz, CDCl3) δ 7.60 (br, 0.15H), 7.44 (br s, 0.5H), 6.51 (0.35H), 5.38 (d, J=5.3 Hz, 0.8H), 5.29 (s, 0.2H), 4.65 (br m, 0.8H), 4.1-4.3 (br m, 1.2H), 3.84 (m, 0.8H), 3.78 (m, 0.2H), 3.59 (m, 1H), 3.25-3.45 (br m, 2H), 2.95 (dd, J=17.6, 7.1 Hz, 0.2H), 2.78 (br m, 0.8H), 2.34 (dd, J=17.2, 10.4 Hz, 0.8H), 1.9-2.3 (br 1.7H), 1.83 (br s, 2.5H), 1.39 (s, 9H), 1.19 (m, 3H) ppm.

Workup

  1. temperaturemaintain a blueish color (˜pH3)
  2. filtrationwas filtered (Celite)
  3. customwas evaporated
  4. dissolutionThe residue was dissolved in dichloromethane (5 mL)
  5. stirringwas stirred at room temperature under nitrogen for 20 h
  6. washwas washed with 10% sodium bisulfate, saturated sodium bicarbonate, and brine
  7. dry with materialwas dried over sodium sulfate
  8. customwas evaporated
  9. customPurification by flash chromatography (SiO2)
  10. washeluted with 1:1 ethyl acetate

Sources & evidence

ORD record
ord-cd35fd98610a4db9b6206170c6a39745
Source dataset
uspto-grants-2006_09
Patent number
US07109357B2

Reaction notes

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