Methanol → Benzyl 4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylate

HRID 1908012Notes

Reaction equation

HRID 1908012 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8](=[O:10])[CH3:9].O=[C:12]1[CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[O:19])[CH2:14][CH2:13]1.N1CCCC1.CO>C(OCC)(=O)C>[O:10]=[C:8]1[C:3]2[C:2](=[CH:7][CH:6]=[CH:5][CH:4]=2)[O:1][C:12]2([CH2:17][CH2:16][N:15]([C:18]([O:20][CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[O:19])[CH2:14][CH2:13]2)[CH2:9]1

Participants

6

Reactant 4

HCID 887MethanolHCID 83752'-HydroxyacetophenoneHCID 31268PyrrolidineHCID 643496Benzyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 30561364Benzyl 4-oxospiro[chroman-2,4'-piperidine]-1'-carboxylateYield 81%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 1-(2-hydroxyphenyl)ethanone (50 g, 0.37 mol), benzyl 4-oxopiperidine-1-carboxylate (94 g, 0.40 mol), pyrrolidine (61 mL, 0.73 mol) and methanol (24 mL) was heated at 80° C. for 20 hours. After cooling to 25° C., the reaction mixture was diluted with ethyl acetate (1000 mL) and partitioned with 1M aqueous HCl (500 mL). The organic phase was washed with 1M aqueous HCl (2×500 mL), water (500 mL), saturated sodium chloride solution (500 mL), dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (0-30% ethyl acetate in hexane) afforded benzyl 4-oxospiro[chroman-2,4′-piperidine]-1′-carboxylate (105 g, 81% yield) as a yellow oil. ESI-MS m/z calc. 351.2. found 352.2 (M+1)+; Retention time: 2.30 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.88 (d, J=7.8 Hz, 1H), 7.54-7.47 (m, 1H), 7.44-7.29 (m, 5H), 7.02 (dd, J=14.8, 7.8 Hz, 2H), 5.16 (s, 2H), 4.10-3.90 (m, 2H), 3.36-3.24 (m, 2H), 2.73 (s, 2H), 2.12-2.00 (m, 2H), 1.71-1.58 (m, 2H).

Workup

  1. temperatureAfter cooling to 25° C.
  2. custompartitioned with 1M aqueous HCl (500 mL)
  3. washThe organic phase was washed with 1M aqueous HCl (2×500 mL), water (500 mL), saturated sodium chloride solution (500 mL)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customPurification by silica gel chromatography (0-30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-bd568f987f5840f8bea4cde8501a94a7
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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