Acetic Acid → HCID 66999388, compound

HRID 655528Notes

Reaction equation

HRID 655528 reaction equation
C(=O)([O-])O.[Na+].[C:6]([O:10][C:11]([N:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21]O)[C:15](=[O:23])[C@@H:14]1[CH3:24])=[O:12])([CH3:9])([CH3:8])[CH3:7].[Br-].[K+].Cl[O-].[Na+].[NH:30]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CC1(C)N([O])C(C)(C)CCC1>[C:6]([O:10][C:11]([N:13]1[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][CH2:21][N:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)[C:15](=[O:23])[C@@H:14]1[CH3:24])=[O:12])([CH3:9])([CH3:8])[CH3:7]

Participants

10

Reactant 7

HCID 176Acetic AcidHCID 8082PiperidineHCID 253877Potassium BromideHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 23665760Sodium HypochloriteHCID 67079693HCID 67079693, compound

Product 1

HCID 66999388HCID 66999388, compoundYield 90.3%

Reagents, catalysts & solvents 2

HCID 2724126TempoCatalystHCID 6344DichloromethaneSolvent2×

Procedure

Saturated aq. sodium hydrogencarbonate solution (1.25 ml) was added to a solution of (S)-4-(3-hydroxy-propyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (1.00 g, 3.67 mmol), potassium bromide (44 mg, 0.37 mmol), and 2,2,6,6-tetramethylpiperidin-1-oxyl (6 mg, 0.04 mmol) in dichloromethane (50 ml). Sodium hypochlorite solution (10% in water, 2.2 ml, 3.7 mmol) was added portionwise at 0° C., and the course of the oxidation was monitored by thin layer chromatography. After all starting material had reacted, the reaction mixture was washed with sat. aq. sodium hydrogencarbonate solution, and the aqueous layer was extracted twice with dichloromethane. The organic phases were pooled, dried (MgSO4), filtered, and evaporated, thus affoding (S)-4-(3-oxo-propyl)-2-methyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (950 mg). This was dissolved in dichloromethane (20 ml) and added over 20 min to a suspension of piperidine (297 mg, 3.49 mmol) triethylamine (353 mg, 3.49 mmol), acetic acid (419 mg, 6.98 mmol) and sodium triacetoxyborohydride (90% purity; 908 mg, 3.85 mmol) in dichloromethane (20 ml). After 16 h the reaction mixture was washed with 2 M aq. sodium carbonate solution, the organic layer was dried (MgSO4), filtered, and evaporated. Chromatography (SiO2; dichloromethane/methanol/25% aq. ammonia solution 90:10:0.25) produced the title compound (1.07 g, 86%). Light yellow oil, MS (ISP)=340.2 (M+H)+.

Workup

  1. customAfter all starting material had reacted
  2. washthe reaction mixture was washed with sat. aq. sodium hydrogencarbonate solution
  3. extractionthe aqueous layer was extracted twice with dichloromethane
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThis was dissolved in dichloromethane (20 ml)
  8. washAfter 16 h the reaction mixture was washed with 2 M aq. sodium carbonate solution
  9. dry with materialthe organic layer was dried (MgSO4)
  10. filtrationfiltered
  11. customevaporated

Sources & evidence

ORD record
ord-a02d0e862f6a4f4d9574e8b3112ff706
Source dataset
uspto-grants-2011_12
Patent number
US08071586B2

Reaction notes

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