Hydrochloride methanol → benzyl (3R,4S)-3-cyclopropylaminomethyl-4-hydroxypyrrolidine-1-carboxylate hydrochloride

HRID 661485Notes

Reaction equation

HRID 661485 reaction equation
[ClH:1].CO.[CH:4]1([NH:7][CH2:8][C@H:9]2[C@H:13]([OH:14])[CH2:12][N:11]([C:15]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:16])[CH2:10]2)[CH2:6][CH2:5]1>C(OCC)(=O)C>[ClH:1].[CH:4]1([NH:7][CH2:8][C@H:9]2[C@H:13]([OH:14])[CH2:12][N:11]([C:15]([O:17][CH2:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[O:16])[CH2:10]2)[CH2:6][CH2:5]1

Participants

4

Reactant 2

HCID 21893726Hydrochloride methanolHCID 59171044benzyl(3R,4S)-3-cyclopropylaminomethyl-4-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 68542811benzyl (3R,4S)-3-cyclopropylaminomethyl-4-hydroxypyrrolidine-1-carboxylate hydrochlorideYield 92%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

42.0 mL of a 10% hydrogen chloride-methanol solution was added dropwise to a solution of benzyl(3R,4S)-3-cyclopropylaminomethyl-4-hydroxypyrrolidine-1-carboxylate (13.9 g, equivalent to 46.4 mmol) in 195 mL of ethyl acetate under stirring at room temperature (crystallization occurred during the addition). Once crystallization took place, the mixture was stirred for 15 minutes at an internal temperature of 20 to 22° C. Subsequently, 390 mL of diisopropyl ether were added dropwise and the mixture was further stirred for 30 minutes. The resulting crystals were collected by filtration and washed with 28 mL of diisopropyl ether. The washed product was dried for 30 minutes by air-blowing and further dried at 60° C. for 2 hours under reduced pressure to give 13.5 g of the title compound as a colorless crystalline powder (92% yield in the 2 steps).

Workup

  1. customcrystallization
  2. additionoccurred during the addition)
  3. customOnce crystallization
  4. stirringthe mixture was stirred for 15 minutes at an internal temperature of 20 to 22° C
  5. additionSubsequently, 390 mL of diisopropyl ether were added dropwise
  6. stirringthe mixture was further stirred for 30 minutes
  7. filtrationThe resulting crystals were collected by filtration
  8. washwashed with 28 mL of diisopropyl ether
  9. customThe washed product was dried for 30 minutes by air-blowing
  10. customfurther dried at 60° C. for 2 hours under reduced pressure

Sources & evidence

ORD record
ord-ea0602a09b4c43f7a54a527feacb5921
Source dataset
uspto-grants-2011_12
Patent number
US08084622B2

Reaction notes

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