HCID 70024926, compound → HCID 11521463, compound

HRID 1168591Notes

Reaction equation

HRID 1168591 reaction equation
[ClH:1].[C:2]([O:10][C@H:11]1[CH2:15][CH2:14][N:13](CC2C=CC=CC=2)[CH2:12]1)(=[O:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>CC(O)C.[Pd]>[ClH:1].[C:2]([O:10][C@H:11]1[CH2:15][CH2:14][NH:13][CH2:12]1)(=[O:9])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

4

Reactant 1

HCID 70024926HCID 70024926, compound

Product 1

HCID 11521463HCID 11521463, compoundYield 86.7%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
55 °C

Procedure

A warm suspension of (S)-3-Benzoyloxy-N-benzyl-pyrrolidine hydrochloride (11.8 Kg, 37.0 mole) in 2-propanol (118 L) at 40° C. was hydrogenated over 10% palladium on carbon (2.35 Kg, 50% water wet) under 50 psig for 12 hours. Upon confirmation of reaction completion, the mixture was filtered over Celite and the latter was rinsed with additional 2-propanol (38 L). The combined filtrate and rise solutions were concentrated by atmospheric distillation (total volume of 35 L). At this stage, diisopropyl ether (105 L) was slowly added over 15 minutes, and the resulting slurry was further stirred at 55° C. for 15 minutes. The reaction mixture was gradually cooled to −10° C., and stirred an additional 2 hours. The solids were isolated by filtration, washed with diisopropyl ether (30 L) and dried under vacuum at 40° C. to provide the title pyrrolidine (7.3 Kg, 86.6%) as a colorless crystalline material. mp 140-141° C.; 1H NMR (400 MHz, d-6 DMSO) δ 9.65 (bs, s, 2H), 8.04-8.01 (m, 2H), 7.68-7.64 (m, 1H), 7.53-7.49 (m, 2H), 5.53-5.51 (m, 1H), 3.42-3.41 (m, 2H), 3.33-3.28 (m, 2H), 2.25-2.15 (m, 2H); 13C NMR (100 MHz, d-6 DMSO) δ 165.8, 134.3, 130.2, 130.0, 129.3, 74.2, 50.4, 43.7, 31.3; MS [(m+1)/z] 192.2.

Workup

  1. customUpon confirmation of reaction completion
  2. filtrationthe mixture was filtered over Celite
  3. washthe latter was rinsed with additional 2-propanol (38 L)
  4. concentrationThe combined filtrate and rise solutions were concentrated by atmospheric distillation (total volume of 35 L)
  5. additionAt this stage, diisopropyl ether (105 L) was slowly added over 15 minutes
  6. temperatureThe reaction mixture was gradually cooled to −10° C.
  7. stirringstirred an additional 2 hours
  8. customThe solids were isolated by filtration
  9. washwashed with diisopropyl ether (30 L)
  10. customdried under vacuum at 40° C.

Sources & evidence

ORD record
ord-9e886189c4e34a79977458f7d9f3dd22
Source dataset
uspto-grants-2003_09
Patent number
US06624313B2

Reaction notes

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