Tetrabutylammonium Fluoride Trihydrate → (3R,4R)-3-[(Cyclopropyl-phenylacetyl-amino)-methyl]-4-(isopropylamino-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158441Notes

Reaction equation

HRID 1158441 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:24]([CH3:26])[CH3:25])C(OCC[Si](C)(C)C)=O)[C@H:10]([CH2:27][N:28]([CH:38]2[CH2:40][CH2:39]2)[C:29](=[O:37])[CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O.O.O.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][NH:14][CH:24]([CH3:25])[CH3:26])[C@H:10]([CH2:27][N:28]([CH:38]2[CH2:39][CH2:40]2)[C:29](=[O:37])[CH2:30][C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

4

Reactant 2

HCID 11726816Tetrabutylammonium Fluoride TrihydrateHCID 59512347(3R,4S)-3-[(Cyclopropyl-phenylacetyl-amino)-methyl]-4-{[isopropyl-(2-trimethylsilanyl-ethoxycarbonyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 59512261(3R,4R)-3-[(Cyclopropyl-phenylacetyl-amino)-methyl]-4-(isopropylamino-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (3R,4S)-3-[(cyclopropyl-phenylacetyl-amino)-methyl]-4-{[isopropyl-(2-trimethylsilanyl-ethoxycarbonyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester (2.55 g, 4.44 mmol) in CH3CN (30 mL) is added tetrabutylammonium fluoride trihydrate (4.34 g, 13.33 mmol) under a nitrogen atmosphere. The reaction mixture is stirred overnight at reflux. The solvent is removed under vacuum and Water and CH2Cl2 are added, the layers are separated and the aqueous one extracted twice with CH2Cl2. The combined organic extracts are dried (Na2SO4), and the solvent is removed in vacuo. The crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH/NH4OH 98:2:1) to give the title product. TLC, Rf (CH2Cl2/MeOH/NH4OH 98:2:1)=0.11. MS (LC-MS): 430.2 [M+H]+; tR (HPLC, C18 column, 20-100% CH3CN/H2O/16 min, 100% CH3CN/1.5 min, CH3CN and H2O containing 0.1% TFA, flow: 1 mL/min): 3.90 min.

Workup

  1. temperatureat reflux
  2. customThe solvent is removed under vacuum and Water and CH2Cl2
  3. additionare added
  4. customthe layers are separated
  5. extractionthe aqueous one extracted twice with CH2Cl2
  6. dry with materialThe combined organic extracts are dried (Na2SO4)
  7. customthe solvent is removed in vacuo
  8. customThe crude product is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH/NH4OH 98:2:1)

Sources & evidence

ORD record
ord-6e29d67b35a7497dad7c002e31e38f03
Source dataset
uspto-grants-2010_10
Patent number
US07807709B2

Reaction notes

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