1-Hydroxybenzotriazole → HCID 57273518, compound

HRID 1601022Notes

Reaction equation

HRID 1601022 reaction equation
Cl.[N:2]1([CH2:7][C@H:8]2[CH2:12][CH2:11][NH:10][CH2:9]2)[CH2:6][CH2:5][CH2:4][CH2:3]1.C(OC(N1CC[C@@H](CO)C1)=O)(C)(C)C.[CH3:27][O:28][C:29]1[CH:57]=[CH:56][C:32]([CH2:33][S:34][C@@H:35]2[CH2:39][N:38]([C:40]([O:42][CH2:43][C:44]3[CH:49]=[CH:48][C:47]([N+:50]([O-:52])=[O:51])=[CH:46][CH:45]=3)=[O:41])[C@H:37]([C:53](O)=[O:54])[CH2:36]2)=[CH:31][CH:30]=1.C(N(C(C)C)CC)(C)C.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[CH3:27][O:28][C:29]1[CH:30]=[CH:31][C:32]([CH2:33][S:34][C@@H:35]2[CH2:39][N:38]([C:40]([O:42][CH2:43][C:44]3[CH:49]=[CH:48][C:47]([N+:50]([O-:52])=[O:51])=[CH:46][CH:45]=3)=[O:41])[C@H:37]([C:53]([N:10]3[CH2:11][CH2:12][C@H:8]([CH2:7][N:2]4[CH2:6][CH2:5][CH2:4][CH2:3]4)[CH2:9]3)=[O:54])[CH2:36]2)=[CH:56][CH:57]=1

Participants

8

Reactant 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 1514340tert-Butyl (3R)-3-(hydroxymethyl)pyrrolidine-1-carboxylateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 15297071(2S,4S)-4-(4-methoxybenzyl)thio-1-(4-nitrobenzyloxycarbonyl)-L-prolineHCID 67589345HCID 67589345, compound

Product 1

HCID 57273518HCID 57273518, compoundYield 34.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3S)-3-(pyrrolidin-1-ylmethyl)pyrrolidine hydrochloride (367 mg), which had been prepared from (3R)-1-tert-butoxycarbonyl-3-hydroxymethylpyrrolidine, in anhydrous dimethylformamide (10 ml), (2S,4S)-4-(4-methoxybenzylthio)-1-(4-nitrobenzyloxycarbonyl)-2-pyrrolidinecarboxylic acid (804 mg), diisopropylethylamine (1.16 ml), 1-hydroxybenzotriazole (243 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (483 mg) were added. The resulting mixture was stirred at room temperature for 10 hours. The solvent was then distilled off under reduced pressure. The residue was dissolved in ethyl acetate. The resulting solution was washed with a saturated aqueous solution of sodium bicarbonate. The organic layer was dried over anhydrous sodium sulfate and then concentrated by evaporation under reduced pressure. The residue was purified by chromatography through a silica gel column (ethyl acetate/methanol=5/1-1/1), whereby (2S,4S)-4-(4-methoxybenzylthio)-2-[(3R)-3-(pyrrolidin-1-ylmethyl)pyrrolidin-1-ylcarbonyl]-1-(4-nitrobenzyloxycarbonyl)pyrrolidine (362 mg) was obtained.

Workup

  1. distillationThe solvent was then distilled off under reduced pressure
  2. dissolutionThe residue was dissolved in ethyl acetate
  3. washThe resulting solution was washed with a saturated aqueous solution of sodium bicarbonate
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated by evaporation under reduced pressure
  6. customThe residue was purified by chromatography through a silica gel column (ethyl acetate/methanol=5/1-1/1)

Sources & evidence

ORD record
ord-180248aeab3b4f47b956a37ef871d2c9
Source dataset
uspto-grants-1999_11
Patent number
US05977097

Reaction notes

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