3-Bromobenzaldehyde → 1,1-dimethylethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazinecarboxylate

HRID 2080308Notes

Reaction equation

HRID 2080308 reaction equation
[CH3:1][C@H:2]1[CH2:7][NH:6][CH2:5][CH2:4][N:3]1[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9].[Br:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH:19]=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)Cl>[Br:15][C:16]1[CH:17]=[C:18]([CH2:19][N:6]2[CH2:5][CH2:4][N:3]([C:8]([O:10][C:11]([CH3:13])([CH3:12])[CH3:14])=[O:9])[C@@H:2]([CH3:1])[CH2:7]2)[CH:21]=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 765833-BromobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 10081508tert-Butyl (2S)-2-methylpiperazine-1-carboxylate

Product 1

HCID 577367121,1-dimethylethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazinecarboxylateYield 81.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1,1-dimethylethyl (2S)-2-methyl-1-piperazinecarboxylate (100 mg, 0.5 mmol) in CH2Cl2 (5 mL) was mixed with 3-bromo benzaldehyde (0.06 mL, 0.5 mmol) and NaB(OAc)3H (0.16 g, 0.75 mmol). The resulting mixture was stirred for 12 hours, diluted with dichloromethane (30 mL) and washed with brine (50 mL). The organic layer was collected, dried over Na2SO4 and concentrated. Separation via a combiflash system then afforded the title compound (150 mg, 81%): LC/MS: m/z, 369 (M+H); 1HNMR (MeOD) δ 1.26 (3H, d), 1.47 (9H, s), 2.0 (1H, m), 2.1 (1H, m), 2.6 (1H, m), 2.8 (1H, m), 3.1 (1H, m), 3.3 (2H, s), 3.4 (1H, m), 3.5 (1H, m), 3.8 (1H, m), 4.2 (1H, m), 4.88 (1H, s), 7.25 (1H, m), 7.3 (1H, m), 7.4 (1H, m), 7.55 (1H, s).

Workup

  1. washwashed with brine (50 mL)
  2. customThe organic layer was collected
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customSeparation via a combiflash system

Sources & evidence

ORD record
ord-435a889393314cd4a1f294f3b451b068
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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