Trimethyl borate → {3-[((3S)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-1-piperazinyl)methyl]phenyl}boronic acid

HRID 2080329Notes

Reaction equation

HRID 2080329 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C@@H:11]([CH3:22])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.[Li]CCCC.[B:28](OC)([O:31]C)[O:29]C.[NH4+].[Cl-]>C1COCC1.O>[CH3:19][C:18]([O:17][C:15]([N:12]1[CH2:13][CH2:14][N:9]([CH2:8][C:4]2[CH:3]=[C:2]([B:28]([OH:31])[OH:29])[CH:7]=[CH:6][CH:5]=2)[CH2:10][C@@H:11]1[CH3:22])=[O:16])([CH3:21])[CH3:20]

Participants

7

Reactant 4

HCID 8470Trimethyl borateHCID 25517Ammonium ChlorideHCID 577367121,1-dimethylethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazinecarboxylateHCID 178418339Butyllithium

Product 1

HCID 25132855{3-[((3S)-4-{[(1,1-dimethylethyl)oxy]carbonyl}-3-methyl-1-piperazinyl)methyl]phenyl}boronic acidYield 103.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1,1-dimethylethyl (2S)-4-[(3-bromophenyl)methyl]-2-methyl-1-piperazine carboxylate (1.8 g, 4.9 mmol) in THF (4.9 mL) was mixed with nBuLi (3.7 mL, 1.6 M in Hexane, 5.9 mmol) at −78° C. and stirred for 30 min before B(OMe)3 (2.2 mL, 19.6 mmol) was added. After addition, the resulting solution was warmed up to room temperature within 2 hours. The mixture was then mixed with saturated aqueous NH4Cl solution (10 mL), stirred for 25 minutes at room temperature, diluted with H2O (5 mL) and extracted with Et2O (2×30 mL). The organic layers were collected, dried over Na2SO4, filtered and concentrated to afford the crude title compound (1.7 g, quantitative yield): LC/MS: m/z 335 (M+H); 1H-NMR (MeOD) δ 1.24 (d, 3H), 1.46 (s, 9H), 2.00 (m, 1H), 2.13 (m, 1H), 2.68 (d, 1H), 2.82 (d, 1H), 3.12 (m, 1H), 3.44 (m, 1H), 3.56 (m, 1H), 3.80 (d, 1H), 4.18 (m, 1H), 7.33 (m, 1H), 7.38 (m, 1H), 7.51 (d, 1H), 7.59 (s, 1H).

Workup

  1. additionwas added
  2. additionAfter addition
  3. extractionextracted with Et2O (2×30 mL)
  4. customThe organic layers were collected
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-6ea1430295e24ef581f8a768487d2084
Source dataset
uspto-grants-2011_04
Patent number
US07932247B2

Reaction notes

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