(R)-benzyl 2-methylpiperazine-1-carboxylate → (R)-benzyl 4-(3-amino-2-fluorobenzyl)-2-methylpiperazine-1-carboxylate

HRID 539720Notes

Reaction equation

HRID 539720 reaction equation
[CH3:1][C@@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9].[NH2:18][C:19]1[C:20]([F:27])=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH:22]=O>C1COCC1>[NH2:18][C:19]1[C:20]([F:27])=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][N:6]1[CH2:5][CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[C@H:2]([CH3:1])[CH2:7]1

Participants

4

Reactant 2

HCID 40424346(R)-benzyl 2-methylpiperazine-1-carboxylateHCID 552821973-Amino-2-fluorobenzaldehyde

Product 1

HCID 58919233(R)-benzyl 4-(3-amino-2-fluorobenzyl)-2-methylpiperazine-1-carboxylateYield 108.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a room temperature solution of (R)-benzyl 2-methylpiperazine-1-carboxylate (1.7 g, 7.2 mmol, 1.0 equiv) and 3-amino-2-fluorobenzaldehyde (1.0 g, 7.2 mmol, 1.0 equiv) in THF (10 mL) was added NaHB(OAc)3 (3.84 g, 18.1 mmol, 2.5 equiv) as a solid in one portion. After stirring at room temperature for 1.5 h, the reaction was complete, as determined by LCMS. The remaining reducing reagent was quenched by the careful addition of aq. satd. NaHCO3, and the mixture was diluted with EtOAc. The layers were separated and the organic layer was washed with aq. satd. NaHCO3 and brine, dried over sodium sulfate and concentrated in vacuo to provide (R)-benzyl 4-(3-amino-2-fluorobenzyl)-2-methylpiperazine-1-carboxylate (2.8 g, >100% mass recovery). The material was used without further purification. LCMS m/z (APCI)=358.5 (M+H).

Workup

  1. customwas quenched by the careful addition of aq. satd
  2. additionNaHCO3, and the mixture was diluted with EtOAc
  3. customThe layers were separated
  4. washthe organic layer was washed with aq. satd
  5. dry with materialNaHCO3 and brine, dried over sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f337ae41161f404ab11a9c13d2009ced
Source dataset
uspto-grants-2014_10
Patent number
US08871768B2

Reaction notes

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