Sodium Thiosulfate → 2-[2-oxo4-(1H-tetrazol-1-yl)-1-pyrrolidinyl]butanamide

HRID 900305Notes

Reaction equation

HRID 900305 reaction equation
[NH:1]1[CH2:5]CCC1=O.O1C=CC(O)=CC1.BrN1C(=O)CCC1=O.[O-]S([O-])(=S)=O.[Na+].[Na+].BrC1C=CNC=1Br.[NH2:36][CH:37]1[CH2:41][N:40]([CH:42]([CH2:46][CH3:47])[C:43]([NH2:45])=[O:44])[C:39](=[O:48])[CH2:38]1.[N-:49]=[N+:50]=[N-].[Na+]>C1COCC1.CC(O)=O>[O:48]=[C:39]1[CH2:38][CH:37]([N:36]2[CH:5]=[N:1][N:50]=[N:49]2)[CH2:41][N:40]1[CH:42]([CH2:46][CH3:47])[C:43]([NH2:45])=[O:44]

Participants

9

Reactant 6

HCID 24477Sodium ThiosulfateHCID 33557Sodium AzideHCID 67184N-bromobutanimide2×HCID 140565522,3-dibromo-1H-PyrroleHCID 22386994HCID 22386994, compoundHCID 66725717HCID 66725717, compound

Product 1

HCID 223870622-[2-oxo4-(1H-tetrazol-1-yl)-1-pyrrolidinyl]butanamide

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Procedure

In a 0.25 L three necked flask under argon with magnetic stirring, a degassed solution of 2S4-pyrol-pyrrolidin-2-one 223 as a single enantiomer (1.18 g, 0.0049 mol.) in THF (35 ml) is cooled to −78° C. and N-Bromosuccinimide (0.877 g, 0.005 mol.) is added by portions. The reaction mixture is stirred for 0.5 h, and the Na2S2O3 (0.9 g) is added to quench the NBS. The reaction mixture is warmed to room temperature, concentrated in vacuo and purified by chromatography on silicagel (EtOH/CH2Cl2: 05/95 (v/v)) to afford, after recrystallisation in MeCN, (2S)-2-[4-(2-bromo-1H-pyrrol-1-yl)-2-oxo-1-pyrrolidinyl]butanamide 234 (1.05 g, 67%) as a white solid. Alternatively, using the same experimental procedure and 2 equiv. of N-Bromo-succinimide, dibromopyrrole 237 can be obtained. 5.8. Synthesis of Tetrazolyl Derivatives Alternatively to § 5.6, reaction of 2-[4-amino-2-oxo-1-pyrrolidinyl]butanamide with triethyl orthoformiate, NaN3 and AcOH provided 2-[2-oxo4-(1H-tetrazol-1-yl)-1-pyrrolidinyl]butanamide 67. 5.9. Synthesis of (4H-1,2,4-triazol-4-yl) Derivatives Alternatively to § 5.6, reaction of 2-[4-amino-2-oxo-1-pyrrolidinyl]butanamides with pyridine and 1,2-bis((dimethylamino)methylene)hydrazine provided 2-[2-oxo-4-(4H-1,2,4-triazol-4-yl)-1-pyrrolidinyl]butanamides 65 and 66.

Workup

  1. customto quench the NBS
  2. concentrationconcentrated in vacuo
  3. custompurified by chromatography on silicagel (EtOH/CH2Cl2: 05/95 (v/v))
  4. customto afford
  5. customafter recrystallisation in MeCN
  6. customcan be obtained

Sources & evidence

ORD record
ord-92a6661dc8ba4266ae8a235ad56c1398
Source dataset
uspto-grants-2008_04
Patent number
US07358276B2

Reaction notes

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