Sulfuric Acid → (3S)-(+)-1-Benzyl-3-aminopyrrolidine

HRID 1699962Notes

Reaction equation

HRID 1699962 reaction equation
[CH2:1]([N:8]1[C:12](=O)[CH2:11][C@H:10]([NH2:14])[C:9]1=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+].S(=O)(=O)(O)O>O1CCCC1>[CH2:1]([N:8]1[CH2:12][CH2:11][C@H:10]([NH2:14])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 4311764Sodium borohydrideHCID 11435648HCID 11435648, compound

Product 1

HCID 1519353(3S)-(+)-1-Benzyl-3-aminopyrrolidineYield 89.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
65 °C

Procedure

Into a 200 ml four-necked flask with a stirrer, a dropping funnel, a Dimroth condenser, and a thermometer, 9.5 g (46.5mmol) of the (S)-1-benzyl-3-aminopyrrolidine-2,5-dione, 50 ml of tetrahydrofuran, and 8.8 g (0.23 mol) of sodium borohydride were introduced, and a solution in which 11.5g (0.12 mol) of 98% sulfuric acid were diluted with 20 ml of tetrahydrofuran was added dropwise over approximately 30 minutes while stirring under an ice-bath, and then stirring was performed for 2 hours. The reaction mixture was heated to 65° C. and was stirred for 2 hours. After the reaction was complete, vacuum concentration was performed. 70 g of water was added for dissolution, and 25 g of concentrated hydrochloric acid were added thereto, followed by stirring at 65° C. for 4 hours. The reaction mixture was cooled to room temperature and was neutralized by adding 32 g of 46% sodium hydroxide while stirring. Extraction was performed three times using 100 ml of toluene, and all the toluene layers were simultaneously subjected to vacuum concentration. The concentrate was subjected to vacuum distillation, and thus 7.3 g of (S)-1-benzyl-3-aminopyrrolidine were obtained as the distillate collected at 130 to 133° C./1.3 kPa. As a result of analysis, the chemical purity was 99% and the optical purity was 91% e.e. 7.0 g of the (S)-1-benzyl-3-aminopyrrolidine, 25 ml of methanol, and 0.7 g of 5% Pd/C were introduced into a 100 ml autoclave, and hydrogen was adjusted to have a pressure of 1 MPa. The temperature was increased to 70° C. and stirring was performed for 8 hours. After the reaction was complete, the temperature was decreased to room temperature and the pressure was released. The content was filtered and the mother liquor was concentrated and distilled, and thus 3.2 g of (S)-3-aminopyrrolidine were obtained as the distillate collected at 80 to 83° C./40 kPa. As a result of analysis, the chemical purity was 99% and the optical purity was 90% e.e.

Workup

  1. additionwas added dropwise over approximately 30 minutes
  2. stirringstirring
  3. stirringwas stirred for 2 hours
  4. concentrationvacuum concentration
  5. addition70 g of water was added for dissolution, and 25 g of concentrated hydrochloric acid
  6. additionwere added
  7. stirringby stirring at 65° C. for 4 hours
  8. temperatureThe reaction mixture was cooled to room temperature
  9. additionby adding 32 g of 46% sodium hydroxide
  10. stirringwhile stirring
  11. extractionExtraction
  12. concentrationall the toluene layers were simultaneously subjected to vacuum concentration
  13. distillationThe concentrate was subjected to vacuum distillation

Sources & evidence

ORD record
ord-3be6427e135746d3bc399d1486a58bbc
Source dataset
uspto-grants-2002_02
Patent number
US06348600B1

Reaction notes

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