1,2-Dichloroethane → HCID 68810136, compound

HRID 2375264Notes

Reaction equation

HRID 2375264 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:15][C:14](=[O:16])[CH2:13][C@H:9]1[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.Cl.[F:32][C:33]1([F:38])[CH2:37][CH2:36][NH:35][CH2:34]1.C(=O)(O)[O-].[Na+]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:15][C:14](=[O:16])[CH2:13][C@H:9]1[C:10]([N:35]1[CH2:36][CH2:37][C:33]([F:38])([F:32])[CH2:34]1)=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 11593804(2S)-1-(tert-butoxycarbonyl)-4-oxopyrrolidine-2-carboxylic acidHCID 249034823,3-Difluoropyrrolidine hydrochloride

Product 1

HCID 68810136HCID 68810136, compoundYield 82.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1-(tert-Butoxycarbonyl)-4-oxo-L-proline (6.88 g, 30 mmol), HOBt (4.46 g, 33 mmol), EDC (6.326 g, 33 mmol), and 3,3-difluoropyrrolidine hydrochloride (4.52 g, 31.5 mmol) were dissolved in 100 mL of dichloromethane and the reaction mixture was cooled to 0° C. in an ice bath before adding TEA (8.4 mL, 60 mmol). The reaction mixture was then allowed to warm to RT. After stirring overnight, saturated sodium bicarbonate (100 mL) was added and the aqueous layer was extracted with dichloromethane. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by chromatography (Biotage® Flash 40M, eluting with 1:10 dichloromethane:hexanes) to afford the title compound 7.85 g (82% yield). MS (El) m/z 319.3 (MH+).

Workup

  1. temperatureto warm to RT
  2. extractionthe aqueous layer was extracted with dichloromethane
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography (Biotage® Flash 40M, eluting with 1:10 dichloromethane:hexanes)

Sources & evidence

ORD record
ord-4d6a5ab3ce77433fb16ca4f61d19cdab
Source dataset
uspto-grants-2008_12
Patent number
US07465732B2

Reaction notes

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