Benzoyl chloride → HCID 59509607, compound

HRID 1423860Notes

Reaction equation

HRID 1423860 reaction equation
C(=O)(O)[O-].[Na+].Cl.[NH2:7][C@@H:8]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:10]([C:20]([O:22][CH3:23])=[O:21])[CH2:9]1.NC1CNC(C(OC)=O)C1.[C:34](Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>CCOC(C)=O.O>[C:34]([NH:7][C@@H:8]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[C@H:10]([C:20]([O:22][CH3:23])=[O:21])[CH2:9]1)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 7412Benzoyl chloride2×HCID 516892Sodium BicarbonateHCID 179989571-tert-Butyl 2-methyl (2S,4S)-4-aminopyrrolidine-1,2-dicarboxylate--hydrogen chloride (1/1)HCID 68512836HCID 68512836, compound

Product 1

HCID 59509607HCID 59509607, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
7.5 °C

Procedure

To a 250-mL three-necked round bottom flask, with mechanical stirring, was charged 4.8 g (56.8 mmol) of sodium bicarbonate followed by 48 mL water. To this stirred solution was charged (2S,4S)-1-tert-butyl 2-methyl 4-aminopyrrolidine-1,2-dicarboxylate hydrochloride A (4 g, 14.2 mmol; prepared from commercially available methyl 4-aminopyrrolidine-2-carboxylate) and EtOAc (40 mL) (two hazy layers observed). The reaction mixture was cooled to 5-10° C. with an ice-bath. Benzoyl chloride (2.0 g, 14.2 mmol) in 8 mL EtOAc was charged dropwise over 10 min maintaining temperature between 5-10° C. The mixture was stirred at 5-10° C. for 1 h and monitored by LC, which showed less than 0.5% by area of benzoyl chloride. The stirring was stopped and the phases were separated. The lower aqueous phase was extracted with EtOAc (2×20 mL). The combined EtOAc layer was washed with 1N HCl (20 mL), saturated NaHCO3 aqueous solution (20 mL), brine (20 mL) and dried with Na2SO4. The EtOAc solution was filtered and the filtrate was evaporated to give 4.87 g of (2S,4S)-1-tert-butyl 2-methyl 4-benzamidopyrrolidine-1,2-dicarboxylate B as a white solid (98.2% yield). NMR conforms to structure. HPLC area percent: 99.3%. 1H NMR (DMSO-d6, δ, ppm): 8.46 (d, J=6.6 Hz, 1H), 7.81 (d, J=8.1 Hz, 2H), 7.56-7.44 (m, 3 H), 4.48-4.41 (m, 1H), 4.27 (t, J=7.8 Hz, 1H), 3.79-3.71 (m, 1H), 3.69 (d, J=11.7, 3 H). 3.34-3.25 (m, 1H), 2.59-2.50 (m, 1H), 2.08-1.99 (m, 1H), 1.38 (d, J=18.9 Hz, 9H). MS (m/z, positive ESI, for M+H): 349.

Workup

  1. temperaturemaintaining temperature between 5-10° C
  2. customthe phases were separated
  3. extractionThe lower aqueous phase was extracted with EtOAc (2×20 mL)
  4. washThe combined EtOAc layer was washed with 1N HCl (20 mL), saturated NaHCO3 aqueous solution (20 mL), brine (20 mL)
  5. dry with materialdried with Na2SO4
  6. filtrationThe EtOAc solution was filtered
  7. customthe filtrate was evaporated

Sources & evidence

ORD record
ord-0847ca3b96e54aa8b434f61ec0d22317
Source dataset
uspto-grants-2015_01
Patent number
US08927590B2

Reaction notes

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