Benzyl Alcohol → HCID 71227049, compound

HRID 2409906Notes

Reaction equation

HRID 2409906 reaction equation
C[C:2]1([C:17](N)=O)[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=2)[CH2:3]1.[C:20]1([CH2:26][OH:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.N12CCCN=C1CCCCC2.Br[N:40]1[C:44](=[O:45])CCC1=O>C(Cl)CCl>[CH3:17][C:2]1([NH:40][C:44](=[O:45])[O:27][CH2:26][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:7][CH2:6][CH2:5][N:4]([C:8]2[CH:9]=[CH:10][C:11]([N+:14]([O-:16])=[O:15])=[CH:12][CH:13]=2)[CH2:3]1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 67184N-bromobutanimide2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 71226405HCID 71226405, compound

Product 1

HCID 71227049HCID 71227049, compoundYield 87.5%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-methyl-1-(4-nitrophenyl)piperidine-3-carboxamide (1.8538 g, 7.04 mmol) and phenylmethanol (7.61 g, 70.4 mmol) in C1CH2CH2Cl (30 ml) cooled at 0° C. was added 1,8-diazabicyclo[5.4.0]undec-7-ene (3.18 mL, 21.12 mmol) dropwise, followed by 1-bromopyrrolidine-2,5-dione (1.378 g, 7.74 mmol) in portions. After addition, the resulting yellow mixture was stirred at 0° C. for 15 min, then at rt for 3.5 hrs, LCMS showed the reaction was not complete and 10% more of NBS (138 mg) was added and the reaction was allowed to stir for an additional 2.5 hrs. The reaction mixture was quenched by addition of water (50 mL) and then adjusted to pH=5 with 1N aqueous HCl. The solution was extracted with EtOAc (3×). The combined EtOAc extracts were washed with water, saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 0-30% EtOAc/Hex to give product, benzyl 3-methyl-1-(4-nitrophenyl)piperidin-3-ylcarbamate (2.274 g, 6.16 mmol, 87% yield) as a yellow oil. Anal. Calcd. for C20H23N3O4 m/z 369.4, found: 370.1 (M+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 8.06 (d, J=9.34 Hz, 2 H), 7.37 (d, J=4.40 Hz, 1 H), 7.34-7.27 (m, 4 H), 6.81 (d, J=9.34 Hz, 2 H), 5.09-4.93 (m, 2 H), 4.74 (s, 1 H), 4.18-4.07 (m, 1 H), 3.74-3.62 (m, 1 H), 3.11-3.02 (m, 2 H), 2.04-1.99 (m, 1 H), 1.81-1.68 (m, 2 H), 1.58-1.51 (m, 1 H), 1.44 (s, 3 H).

Workup

  1. additionAfter addition
  2. waitat rt for 3.5 hrs
  3. stirringto stir for an additional 2.5 hrs
  4. customThe reaction mixture was quenched by addition of water (50 mL)
  5. extractionThe solution was extracted with EtOAc (3×)
  6. washThe combined EtOAc extracts were washed with water, saturated aqueous NaCl
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe resulting residue was purified
  11. washeluting with a gradient of 0-30% EtOAc/Hex

Sources & evidence

ORD record
ord-54be43ba6cfa452fb9c2ba2fc9c049f7
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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