Diisopropylethylamine → HCID 69067080, compound

HRID 1912489Notes

Reaction equation

HRID 1912489 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][C:9]2([CH3:15])[CH3:14])=[CH:4][CH:3]=1.[C:16]([O:20][C:21]([NH:23][C@H:24]([CH:28]([CH3:30])[CH3:29])[C:25](O)=[O:26])=[O:22])([CH3:19])([CH3:18])[CH3:17].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:25](=[O:26])[C@H:24]([NH:23][C:21](=[O:22])[O:20][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:28]([CH3:30])[CH3:29])[CH2:10][C:9]2([CH3:15])[CH3:14])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acidHCID 20099412HCID 20099412, compound

Product 1

HCID 69067080HCID 69067080, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(4-chlorophenyl)-2,2-dimethylpiperazine (0.76 g, 3.38 mmol) in DMF (10 mL), was added (R)-2-(tert-butoxycarbonylamino)-3-methylbutanoic acid (0.735 g, 3.38 mmol), BOP (1.496 g, 3.38 mmol) and DIPEA (0.588 mL, 3.38 mmol). The mixture was stirred at rt for 2 h, quenched with aq. NaHCO3, extracted with EtOAc, and washed with brine. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by a flash column chromatography using 30% EtOAc in hexanes as an eluent. The product containing fractions were concentrated and dried to give (R)-tert-butyl 1-(4-(4-chlorophenyl)-3,3-dimethylpiperazin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate (1.36 g, 3.21 mmol, 95% yield) as a yellow oil. To (R)-tert-butyl 1-(4-(4-chlorophenyl)-3,3-dimethylpiperazin-1-yl)-3-methyl-1-oxobutan-2-ylcarbamate was added 4N HCL in dioxane and the resulting mixture stirred at room temperature until the starting material had been consumed. The volatile solvents were removed and the product dried to give (R)-2-Amino-1-(4-(4-chlorophenyl)-3,3-dimethylpiperazin-1-yl)-3-methylbutan-1-one hydrochloride as a white solid.

Workup

  1. customquenched with aq. NaHCO3
  2. extractionextracted with EtOAc
  3. washwashed with brine
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by a flash column chromatography
  8. additionThe product containing fractions
  9. concentrationwere concentrated
  10. customdried

Sources & evidence

ORD record
ord-d666361b492f4706aeb483c1bba293fb
Source dataset
uspto-grants-2013_12
Patent number
US08609664B2

Reaction notes

Loading…