Acetic Acid → HCID 59452658, compound

HRID 419441Notes

Reaction equation

HRID 419441 reaction equation
[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][C:13](=O)[CH2:12][CH2:11]2)=[CH:6][C:5]=1[O:17][CH2:18][C:19]([F:22])([F:21])[F:20])([O-:3])=[O:2].CC(O)=O.[C:27]([N:34]1[CH2:39][CH2:38][NH:37][CH2:36][CH2:35]1)([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(#N)C.C1(C)C=CC=CC=1>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([N:37]3[CH2:36][CH2:35][N:34]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:39][CH2:38]3)[CH2:12][CH2:11]2)=[CH:6][C:5]=1[O:17][CH2:18][C:19]([F:22])([F:21])[F:20])([O-:3])=[O:2]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 143452tert-Butyl piperazine-1-carboxylateHCID 5049666Sodium triacetoxyborohydrideHCID 59452684HCID 59452684, compound

Product 1

HCID 59452658HCID 59452658, compoundYield 54%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 6342AcetonitrileSolvent2×

Procedure

1-{4-Nitro-3-[(2,2,2-trifluoroethyl)oxy]phenyl}-4-piperidinone (1.63 g, 5.12 mmol) was dissolved in 20 mL of acetonitrile with stirring. HOAc (0.44 mL, 7.7 mmol) was added, and 20 mL of toluene was added. TEA (1.78 mL, 12.8 mmol) was added followed by 1-BOC-piperazine (1.91 g, 10.3 mmol). Sodium triacetoxyborohydride (2.71 g, 12.8 mmol) was added. After 1 h, 40 mL of acetonitrile and 20 mL of toluene were added, and the reaction was stirred overnight. The reaction was quenched with 1N NaOH and poured into H2O and EtOAc. The layers were separated, and the organic layer was washed with brine. The combined aqueous layers were extracted with EtOAc. The combined organic layers was dried over MgSO4, filtered, and concentrated in vacuo. Purification by flash chromatography afforded 1.35 g (54%) of the title compound of step D. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.85 (d, J=9.5 Hz, 1H), 6.63 (dd, J=9.6, 2.3 Hz, 1H), 6.56 (d, J=2.2 Hz, 1H), 4.88 (q, J=8.7 Hz, 2H), 3.98-4.10 (m, 2H), 3.27 (s, 4H), 2.84-2.97 (m, 2H), 2.33-2.55 (m, 5H), 1.76 (br. s., 2H), 1.29-1.45 (m, 11H).

Workup

  1. stirringthe reaction was stirred overnight
  2. customThe reaction was quenched with 1N NaOH
  3. additionpoured into H2O and EtOAc
  4. customThe layers were separated
  5. washthe organic layer was washed with brine
  6. extractionThe combined aqueous layers were extracted with EtOAc
  7. dry with materialThe combined organic layers was dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by flash chromatography

Sources & evidence

ORD record
ord-bf115ea0872246e190c519f597059941
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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