Triethylamine → {1-[(1S)-1-(aminocarbonyl)propyl]-5-oxo-3-pyrrolidinyl}methyl 4-methylbenzenesulfonate

HRID 900310Notes

Reaction equation

HRID 900310 reaction equation
[OH:1][CH2:2][CH:3]1[CH2:7][N:6]([C@@H:8]([CH2:12][CH3:13])[C:9]([NH2:11])=[O:10])[C:5](=[O:14])[CH2:4]1.[CH2:15](N(CC)CC)C.[CH3:22][S:23](Cl)(=[O:25])=[O:24].N([CH2:30][CH:31]1[CH2:35]N([C@@H](CC)C(N)=O)[C:33](=O)[CH2:32]1)=[N+]=[N-]>C(Cl)Cl>[CH3:35][C:31]1[CH:30]=[CH:15][C:22]([S:23]([O:1][CH2:2][CH:3]2[CH2:4][C:5](=[O:14])[N:6]([C@H:8]([C:9]([NH2:11])=[O:10])[CH2:12][CH3:13])[CH2:7]2)(=[O:25])=[O:24])=[CH:33][CH:32]=1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chloride2×HCID 60105793(2S)-2-[4-(azidomethyl)-2-oxo-1-pyrrolidinyl]butanamideHCID 60105803(2S)-2-[4-(hydroxymethyl)2-oxo-1-pyrrolidinyl]butanamide

Product 1

HCID 10291696{1-[(1S)-1-(aminocarbonyl)propyl]-5-oxo-3-pyrrolidinyl}methyl 4-methylbenzenesulfonate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

In a 4 l three necked flask fitted with mechanical stirrer, dropping funnel and reflux condenser under inert atmosphere, 114 g (569 mmoles, 1 eq) of (2S)-2-[4-(hydroxymethyl)-2-oxo-1-pyrrolidinyl]butanamide 6 are dissolved in 2 l of CH2Cl2 and cooled down to 0° C. 158.5 ml (115 g, 2 eq) of dry triethylamine are added in one portion, followed by dropwise addition of a solution of 66.3 ml (96.2 g, 1.5 eq) of methanesulfonyl chloride in 190 ml of CH2Cl2 over 1 hour, all the while maintaining the temperature below 4° C. After 4 hours, 7.5 ml of methanesulfonyl chloride and 15 ml of triethylamine are added and the mixture is kept overnight in the refrigerator. The mixture is filtered, the residue washed with CH2Cl2 and the combined organic phases concentrated to dryness to give 216 g of crude 37. It is purified by Prep LC in several batches (1 kg SiO2, CH2Cl2/EtOH, 100:0->96:4) to give 109 g of pure 37, 69%. Alternatively, {1-[(1S)-1-(aminocarbonyl)propyl]-5-oxo-3-pyrrolidinyl}methyl 4-methylbenzenesulfonate 31 is prepared in an analogous way. 7.2.2. Synthesis of (2S)-2-[4-(azidomethyl)-2-oxo-1-pyrrolidinyl]butanamide 32

Workup

  1. temperatureall the while maintaining the temperature below 4° C
  2. waitthe mixture is kept overnight in the refrigerator
  3. filtrationThe mixture is filtered
  4. washthe residue washed with CH2Cl2
  5. concentrationthe combined organic phases concentrated to dryness
  6. customto give 216 g of crude 37
  7. customIt is purified by Prep LC in several batches (1 kg SiO2, CH2Cl2/EtOH, 100:0->96:4)
  8. customto give 109 g of pure 37, 69%

Sources & evidence

ORD record
ord-32340ce2e42d4563bbdaf51e8f3f23ff
Source dataset
uspto-grants-2008_04
Patent number
US07358276B2

Reaction notes

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