tert-Butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate → tert-Butyl (3R)-4-[2-(4-cyano-3-methoxyphenyl)-2-hydroxyethyl]-3 (hydroxymethyl)piperazine1-carboxylate

HRID 1502064Notes

Reaction equation

HRID 1502064 reaction equation
[CH3:1][O:2][C:3]1[CH:10]=[C:9]([CH:11]2[CH2:13][O:12]2)[CH:8]=[CH:7][C:4]=1[C:5]#[N:6].[OH:14][CH2:15][C@@H:16]1[NH:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1>CCO>[C:5]([C:4]1[CH:7]=[CH:8][C:9]([CH:11]([OH:12])[CH2:13][N:21]2[CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:23])[CH2:17][C@@H:16]2[CH2:15][OH:14])=[CH:10][C:3]=1[O:2][CH3:1])#[N:6]

Participants

4

Reactant 2

HCID 24820286tert-Butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylateHCID 552967592-Methoxy-4-(oxiran-2-yl)benzonitrile

Product 1

HCID 86727084tert-Butyl (3R)-4-[2-(4-cyano-3-methoxyphenyl)-2-hydroxyethyl]-3 (hydroxymethyl)piperazine1-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A Pyrex vessel was charged with magnetic stirring bar, (2.0 g, 11.42 mmol) of 2-methoxy-4-(oxiran-2-yl)benzonitrile, (3.70 g, 17.12 mmol) of tert-butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate, and 6 mL of EtOH. Then it was introduced in the microwave reactor and irradiated at 150° C. for 3 h. The mixture was cooled to room temperature and the solvent was evaporated and the resulting residue was purified by column chromatography (silica gel, 1-20% dichloromethane/MeOH) which afforded the product as a mixture of two diastereomers (1:1) LC/MS: (IE, m/z) [(M+1)-t-Bu]+=336.41

Workup

  1. additionA Pyrex vessel was charged with magnetic stirring bar
  2. additionThen it was introduced in the microwave reactor
  3. customirradiated at 150° C. for 3 h
  4. customthe solvent was evaporated
  5. customthe resulting residue was purified by column chromatography (silica gel, 1-20% dichloromethane/MeOH) which
  6. customafforded the product
  7. additionas a mixture of two diastereomers (1:1) LC/MS

Sources & evidence

ORD record
ord-40d9f6ccc95d4247bd0d107c5bdeb083
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

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