Phthalimide → (2S)-1-[(3-aminophenyl)methoxy]-propan-2-ol

HRID 1385316

Reaktionsgleichung

Reaktionsgleichung von HRID 1385316
CN[C@@H:3]([CH3:14])[CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([NH2:13])[CH:8]=1.NC1C=C(C=CC=1)C[OH:20].C1(=O)NC(=O)C2=CC=CC=C12.BrCC(O)C.BrC[C@H](C)OC1CCCCO1.[H-].[Na+]>O1CCCC1.CN(C)C=O>[NH2:13][C:9]1[CH:8]=[C:7]([CH2:6][O:5][CH2:4][C@@H:3]([OH:20])[CH3:14])[CH:12]=[CH:11][CH:10]=1

Komponenten

9

Edukt 6

HCID 6809PhthalimideHCID 24758Sodium hydrideHCID 297401-Bromo-2-propanolHCID 802933-Aminobenzyl alcoholHCID 15624992(1S)-2-(2-bromo-1-methylethoxy)tetrahydro-2H-pyranHCID 57117145HCID 57117145, Verbindung

Produkt 1

HCID 57246812(2S)-1-[(3-aminophenyl)methoxy]-propan-2-ol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

The manner in which optically active forms of arylmethoxy aliphatic amines, such as (2S)-N-methyl-1-[(3-aminophenyl)methoxy]-propan-2-amine type compounds, are providcd can vary. In one approach, a 3-aminobenzyl alcohol type compound (N-protected as the phthalimide) can be alkylated with a chiral 1-bromo-2-propanol type compound containing an O-protecting group, such as (1S)-2-(2-bromo-1-methylethoxy)tetrahydro-2H-pyran using a base such as sodium hydride and a solvent such as N,N-dimethylformamide or tetrahydrofuran. The tetrahydropyranyl protecting group of the resulting chiral arylmethyl ether type compound can be removed with aqueous sulfuric acid in methanol, affording (2S)-1-[(3-aminophenyl)methoxy]-propan-2-ol. The resulting chiral alcohol intermediate can be converted to its corresponding tosylate, followed by tosylate displacement with methylamine with inversion of configuration, and finally removal of the N-phthaloyl group to give the chiral amine (2R)-N-methyl-1-[(3-aminophenyl)methoxy]-propan-2-amine. Chiral side chain compounds such as (1S)-2-(2-bromo-1-methylethoxy)tetrahydro-2H-pyran can be prepared from (2S)-1-bromo-2-propanol by treatment with 3,4-dihydro-211-pyran in dichloromethane with p-tolucnesulfonic acid as a catalyst according to the method of S. A. M. Nieuwenhuis et al., Tetrahedron 50: 13207-13230 (1994). The required (2S)-l-bromo-2-propanol can be obtained from (S)-propylene oxide (commercially available from Fluka) by treatment with hydrogen bromide in acetic acid at 0° C. The corresponding optical antipode, (2R)-N-methyl-1-[(3-aminophenyl)methoxy]-propan-2-amine can be prepared in an analogous manner from (R)-propylene oxide (commercially available from Fluka) by using the synthetic procedure of S. A. M. Nieuwenhuis et al. to prepare the tetrahydropyranyl ether of (2R)-1-bromo-2-propanol and by using the synthetic sequence described above.

Aufarbeitung

  1. additioncontaining an O-protecting group
  2. customThe tetrahydropyranyl protecting group of the resulting chiral arylmethyl ether type compound can be removed with aqueous sulfuric acid in methanol

Quellen und Nachweise

ORD-Eintrag
ord-5c7d86659820427c9f95fec3fb12f65f
Quelldatensatz
uspto-grants-2001_07
Patentnummer
US06262124B1

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