1-Hydroxybenzotriazole → (2S)-2-{(1R,2S)-2-[2-(3-hydroxy-phenyl)-ethylcarbamoyl]-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1582735Notes

Reaction equation

HRID 1582735 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C@H:13]([S:19][CH3:20])[C@H:14]([C:16]([OH:18])=O)[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br.[OH:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][CH:31]=1)[CH2:26][CH2:27][NH2:28].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C@H:13]([S:19][CH3:20])[C@H:14]([C:16](=[O:18])[NH:28][CH2:27][CH2:26][C:25]1[CH:29]=[CH:30][CH:31]=[C:23]([OH:22])[CH:24]=1)[CH3:15])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 11522334(2S)-2-[(R,2S)-2-carboxy-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 227178563-(2-Aminoethyl)phenol hydrobromide

Product 1

HCID 69551291(2S)-2-{(1R,2S)-2-[2-(3-hydroxy-phenyl)-ethylcarbamoyl]-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 87.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of (2S)-2-[(1R,2S)-2-carboxy-1-methylsulfanyl-propyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (1.7 g, 5.6 mmol) in CH2Cl2 (20 mL) were added 3-hydroxyphenethylamine hydrobromide (2.44 g, 11.2 mmol), BOP(3.72 g, 8.4 mmol), HOBT (1.29 g, 8.4 mmol), and diisopropylethylamine (4.88 mL, 28.0 mmol) at room temperature. After being stirred at room temperature for 2 hr, the mixture was quenched with 1N HCl (80 mL×3), extracted with AcOEt, dried (MgSO4) and concentrated in vacuo to give a crude oil, which was purified by flash column chromatography (hexane:AcOEt=1:1) to give (2S)-2-{(1R,2S)-2-[2-(3-hydroxy-phenyl)-ethylcarbamoyl]-1-methylsulfanyl-propyl}-pyrrolidine-1-carboxylic acid tert-butyl ester as a gum (2.07 g, 87%).

Workup

  1. customthe mixture was quenched with 1N HCl (80 mL×3)
  2. extractionextracted with AcOEt
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customto give a crude oil, which
  6. customwas purified by flash column chromatography (hexane:AcOEt=1:1)

Sources & evidence

ORD record
ord-843db06507cd4bf590471b7a274ebb05
Source dataset
uspto-grants-2004_05
Patent number
US06737409B2

Reaction notes

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