Methylamine → (3R*,4R*)-3-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1158341Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1158341
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[C@H:10]([CH:34]=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].S([O-])([O-])(=O)=O.[Mg+2].[CH3:42][NH2:43].[BH4-].[Na+]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][C@@H:10]([CH2:34][NH:43][CH3:42])[C@H:11]([CH2:13][N:14]([CH:31]([CH3:33])[CH3:32])[C:15](=[O:30])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH:17]=2)[CH2:12]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Komponenten

6

Edukt 4

HCID 6329MethylamineHCID 24083Sulfuric acid magnesium salt (1:1)HCID 4311764Sodium borohydrideHCID 59512275(3S*,4R*)-3-formyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Produkt 1

HCID 59512501(3R*,4R*)-3-({Isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-4-methylaminomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of (3S*,4R*)-3-formyl-4-({isopropyl-[4-methoxy-3-(3-methoxy-propoxy)-benzoyl]-amino}-methyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (150 mg, 0.304 mmol) and magnesium sulfate (92 mg, 0.373 mmol) in THF (4 mL), methylamine (1.52 mL, 3.044 mmol, 2M in THF) is added. The solution is stirred at RT overnight under nitrogen atmosphere and NaBH4 (23 mg, 0.608 mmol) is added. The resulting mixture is stirred for 1 h and the excess reducing agent quenched with water, CH2Cl2 is added and the reaction mixture is poured into an aqueous saturated solution of NaHCO3. The organic layer is separated and the aqueous phase extracted twice with CH2Cl2, dried over Na2SO4, filtered, and concentrated in vacuo. The crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 95:5+1% NH4OH ) to give the title product. TLC, Rf (CH2Cl2/MeOH 95:5)=0.05. MS (LC-MS) [M−H]+=508.1. tR (HPLC, Nucleosil C18 column, 10-100% CH3CN/H2O/5 min, 100% CH3CN/3 min, CH3CN and H2O containing 0.1% TFA, flow: 1.5 ml/min): 4.53 min.

Aufarbeitung

  1. stirringThe resulting mixture is stirred for 1 h
  2. customquenched with water, CH2Cl2
  3. additionis added
  4. additionthe reaction mixture is poured into an aqueous saturated solution of NaHCO3
  5. customThe organic layer is separated
  6. extractionthe aqueous phase extracted twice with CH2Cl2
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe crude material is purified by flash chromatography on silica gel (eluent: CH2Cl2/MeOH 100:0 to 95:5+1% NH4OH )

Quellen und Nachweise

ORD-Eintrag
ord-f19e11325e144320ad0c76b64dd40892
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807709B2

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