tert-Butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylate → (3R)-tert-butyl 4-(2-(3-cyano-2,4-difluorophenyl)-2-hydroxyethyl)-3-(hydroxymethyl)piperazine-1-carboxylate

HRID 1502014Notes

Reaction equation

HRID 1502014 reaction equation
[F:1][C:2]1[C:9]([CH:10]2[CH2:12][O:11]2)=[CH:8][CH:7]=[C:6]([F:13])[C:3]=1[C:4]#[N:5].[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>C(O)C>[C:4]([C:3]1[C:2]([F:1])=[C:9]([CH:10]([OH:11])[CH2:12][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:8]=[CH:7][C:6]=1[F:13])#[N:5]

Participants

4

Reactant 2

HCID 24820286tert-Butyl (3R)-3-(hydroxymethyl)piperazine-1-carboxylateHCID 867270612,6-Difluoro-3-(oxiran-2-yl)benzonitrile

Product 1

HCID 86727064(3R)-tert-butyl 4-(2-(3-cyano-2,4-difluorophenyl)-2-hydroxyethyl)-3-(hydroxymethyl)piperazine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2,6-difluoro-3-(oxiran-2-yl)benzonitrile (3.70 g, 20.4 mmol) and (R)-tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (6.63 g, 30.6 mmol) were dissolved in ethanol (36.0 mL) then placed in 3-20 mL sealed tubes and microwaved at 140° C. for 1 h. The solvents were evaporated and the combined residue was purified by chromatography through a 120 g ISCO Redi-sep column with 50% to 100% ethyl acetate/hexane solvent system to yield the title compound LC-MS (IE, m/z): 398 [M+1]+.

Workup

  1. customsealed tubes
  2. custommicrowaved at 140° C. for 1 h
  3. customThe solvents were evaporated
  4. customthe combined residue was purified by chromatography through a 120 g ISCO Redi-sep column with 50% to 100% ethyl acetate/hexane solvent system

Sources & evidence

ORD record
ord-bdb425e1391f4369999f0cec3910f382
Source dataset
uspto-grants-2015_12
Patent number
US09206199B2

Reaction notes

Loading…