Hydrochloric Acid → 2-Hydroxy-2-methyl-1-(piperazin-1-yl)propan-1-one

HRID 1453405Notes

Reaction equation

HRID 1453405 reaction equation
C1C2C3=CC4C=CC(C(N)=O)=CC=4N3CC=CC=2C=CC=1.[N:22]1([C:28]([O:30]C(C)(C)C)=O)[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.[OH:35][C:36](C)([CH3:40])[C:37](O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.O.C(N(CC)CC)C>[OH:35][C:36]([CH3:40])([CH3:37])[C:28]([N:22]1[CH2:23][CH2:24][NH:25][CH2:26][CH2:27]1)=[O:30]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 116712-Hydroxyisobutyric acidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 666396907H-indolo[2,1-a][2]benzazepine-10-carboxamide

Product 1

HCID 219492932-Hydroxy-2-methyl-1-(piperazin-1-yl)propan-1-oneYield 319.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

7H-Indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-[[4-(2-hydroxy-2-methyl-l-oxopropyl)-1-piperazinyl]carbonyl]-3-methoxy-. To a solution of tert-butyl piperazine-1-carboxylate (372 mg, 2.0 mmol), 2-hydroxy-2-methylpropanoic acid (229 mg, 2.2 mmol) and triethylamine (1.1 mL) in DMF (7 mL) was added HATU (988 mg, 2.6 mmol). The reaction mixture was stirred at rt for 2 h, then diluted with H2O, neutralized with 1N aqueous HCl (8 mL), concentrated, and the residue was partitioned between EtOAc and H2O. The organic phase was separated, washed with brine and concentrated to a white solid (1.1 g). The solid was dissolved into ClCH2CH2Cl (10 mL) and treated with trifluoroacetic acid (5 mL). The reaction mixture was stirred at rt for 2 h, and concentrated to yield crude 2-hydroxy-2-methyl-1-(piperazin-1-yl)propan-1-one (1.1 g) as yellow semi-solid.

Workup

  1. concentrationconcentrated
  2. customthe residue was partitioned between EtOAc and H2O
  3. customThe organic phase was separated
  4. washwashed with brine
  5. concentrationconcentrated to a white solid (1.1 g)
  6. dissolutionThe solid was dissolved into ClCH2CH2Cl (10 mL)
  7. additiontreated with trifluoroacetic acid (5 mL)
  8. stirringThe reaction mixture was stirred at rt for 2 h
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-884d6eb3ffa449299790b9d12467b7cb
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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