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

HRID 1276391ノート

反応式

HRID 1276391 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][OH:6].C1(=O)NC(=O)C2=CC=CC=C12.Br[CH2:22][CH:23]([OH:25])[CH3:24].BrC[C@H](C)OC1CCCCO1.[H-].[Na+]>O1CCCC1.CN(C)C=O>[NH2:1][C:2]1[CH:3]=[C:4]([CH2:5][O:6][CH2:22][C@@H:23]([OH:25])[CH3:24])[CH:7]=[CH:8][CH:9]=1

参加物

8

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

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 provided 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-2H-pyran in dichloromethane with p-toluenesulfonic acid as a catalyst according to the method of S. A. M. Nieuwenhuis et al., Tetrahedron 50: 13207-13230 (1994). The required (2S)-1-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.

後処理

  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

出典と根拠

ORDレコード
ord-47045181dc884034b65364ccd55ee287
出典データセット
uspto-grants-2000_12
特許番号
US06166048

反応ノート

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