1-Hydroxybenzotriazole → (2s)-2-((1r,2s)-2-{[2-(3-Hydroxy-phenyl)-ethyl]-methyl-carbamoyl}-1-methylsulfanyl-propyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1582736Notes

Reaction equation

HRID 1582736 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.[CH3:22][NH:23][CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=1.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])[N:23]([CH2:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[C:28]([OH:32])[CH:27]=1)[CH3:22])[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 227178343-(2-(Methylamino)ethyl)phenol hydrobromide

Product 1

HCID 58671475(2s)-2-((1r,2s)-2-{[2-(3-Hydroxy-phenyl)-ethyl]-methyl-carbamoyl}-1-methylsulfanyl-propyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 56.4%

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 (1.70 g, 5.6 mmol) in CH2Cl2 (20 mL) were added N-methyl-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 (3.83 g), which was then purified by flash column chromatography (hexane:AcOEt=1:1) to give (2S)-2-((1R,2S)-2-{[2-(3-hydroxy-phenyl)-ethyl]-methyl-carbamoyl}-1-methylsulfanyl-propyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a gum (1.38 g, 56%).

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 (3.83 g), which
  6. customwas then purified by flash column chromatography (hexane:AcOEt=1:1)

Sources & evidence

ORD record
ord-0f59efc7d85f4979bb7cff607902c26e
Source dataset
uspto-grants-2004_05
Patent number
US06737409B2

Reaction notes

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