Hydrochloric Acid → HCID 70819237, compound

HRID 331520Notes

Reaction equation

HRID 331520 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14][CH2:13][N:12]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:7][CH:6]=1)=O.[BH4-].[Li+].Cl.C(=O)(O)[O-].[Na+]>O1CCCC1>[OH:2][CH2:3][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][N:15]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:14][CH2:13][N:12]2[C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 4148881Lithium borohydrideHCID 70818951HCID 70818951, compound

Product 1

HCID 70819237HCID 70819237, compoundYield 78.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

Di tert-butyl 2-(4-methoxycarbonylphenyl)piperazine-1,4-dicarboxylate (1.03 g, 2.449 mmol) was dissolved in tetrahydrofuran (10.30 mL) and lithium boranuide (106.7 mg, 4.898 mmol) was added portion wise. The reaction was heated at 65° C. over 18 hours. The reaction mixture was cooled to ambient temperature then poured onto crushed ice and whilst stirring 1 M hydrochloric acid was added drop wise until no effervescence was observed. The mixture was stirred for 1 hour then saturated aqueous sodium bicarbonate was added until the mixture was at pH 8. The aqueous layer was extracted with ethyl acetate (×3) and the combined organic extracts were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. Purified by column chromatography (ISCO Companion, 40 g column) loaded with dichloromethane and eluted with 10 to 100% ethyl acetate/petroleum ether. Product fractions were combined and concentrated in vacuo to give the sub-title product as a white solid. (754 mg, 78.4% yield). 1H NMR (400.0 MHz, CDCl3) δ 1.45-1.48 (m, 18H), 2.99 (br s, 2H), 3.33-3.37 (m, 1H), 3.95-3.98 (m, 2H), 4.45-4.48 (m, 1H), 4.70 (d, 2H), 5.30 (br s, 1H) and 7.33-7.35 (m, 4H) ppm; TLC (petroleum ether:ethyl acetate, 1:1 v/v) Rf=0.48

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. additionthen poured
  3. customonto crushed ice
  4. additionwas added drop wise until no effervescence
  5. extractionThe aqueous layer was extracted with ethyl acetate (×3)
  6. washthe combined organic extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurified by column chromatography (ISCO Companion, 40 g column)
  11. washeluted with 10 to 100% ethyl acetate/petroleum ether
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1ae8911770ff4a738f384640f4bacf1d
Source dataset
uspto-grants-2014_11
Patent number
US08877759B2

Reaction notes

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