Diisopropylethylamine → Tert-butyl 4-(5-benzylpyrimidin-2-yl)-3-(hydroxymethyl)piperazine-1-carboxylate

HRID 522685Notes

Reaction equation

HRID 522685 reaction equation
[CH2:1]([C:8]1[CH:9]=[N:10][C:11](Cl)=[N:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH:15][CH2:16][CH:17]1[NH:22][CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:18]1.C(N(C(C)C)CC)(C)C>O1CCOCC1>[CH2:1]([C:8]1[CH:9]=[N:10][C:11]([N:22]2[CH2:21][CH2:20][N:19]([C:23]([O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[O:24])[CH2:18][CH:17]2[CH2:16][OH:15])=[N:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 223865084-N-Boc-2-hydroxymethylpiperazineHCID 866373985-Benzyl-2-chloropyrimidine

Product 1

HCID 118023191Tert-butyl 4-(5-benzylpyrimidin-2-yl)-3-(hydroxymethyl)piperazine-1-carboxylateYield 22.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 5-benzyl-2-chloropyrimidine (944 mg, 4.626 mmol), tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (1.0 g, 6.939 mmol) and diisopropylethylamine (1.8 g, 13.878 mmol) in dioxane (100 mL) was stirred at 110° C. for two days. The reaction mixture was cooled to room temperature, concentrated and directly purified by silica gel chromatography eluting with petroleum ether:ethyl acetate=1:1, to afford tert-butyl 4-(5-benzylpyrimidin-2-yl)-3-(hydroxymethyl)piperazine-1-carboxylate (400 mg, 15%) as a white solid. MS (ES+) C21H28N4O3 requires: 384, found: 385 [M+H]+.

Workup

  1. concentrationconcentrated
  2. customdirectly purified by silica gel chromatography
  3. washeluting with petroleum ether

Sources & evidence

ORD record
ord-61f54f680fb0434b90538f00bdbf2d60
Source dataset
uspto-grants-2016_05
Patent number
US09334263B2

Reaction notes

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