2'-Hydroxyacetophenone → Tert-butyl 4-oxo-3,4-dihydrospiro[1-benzopyran-2,4'-piperidine]-1'-carboxylate

HRID 1908003Notes

Reaction equation

HRID 1908003 reaction equation
[O:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.N1CCCC1.O[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[C:27](=[O:29])[CH3:28]>CO.CCCCCC>[O:29]=[C:27]1[C:22]2[C:21](=[CH:26][CH:25]=[CH:24][CH:23]=2)[O:1][C:2]2([CH2:3][CH2:4][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:6][CH2:7]2)[CH2:28]1

Participants

6

Reactant 3

HCID 83752'-HydroxyacetophenoneHCID 31268PyrrolidineHCID 735900tert-Butyl 4-oxopiperidine-1-carboxylate

Product 1

HCID 40427565Tert-butyl 4-oxo-3,4-dihydrospiro[1-benzopyran-2,4'-piperidine]-1'-carboxylateYield 70.7%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8058HexaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of tert-butyl 4-oxopiperidine-1-carboxylate (93.7 g, 470 mmol) in pyrrolidine (56.0 mL, 673 mmol) and anhydrous MeOH (112 mL) was added 1-(2-hydroxyphenyl)ethanone (56 mL, 468 mmol). The reaction mixture was stirred at 80° C. for 2.5 hours. Methanol was removed under reduced pressure. The resulting residue was dissolved in ethyl acetate (150 mL), washed with 1M aqueous HCl (1×150 mL) and brine (2×100 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to afford a yellow oil. This oil was diluted with hexane (400 mL) and was heated at 60° C. until in solution. Once dissolved, the solution was allowed to cool to 25° C. Crystals were collected via vacuum filtration and rinsed with hexane to obtain tert-butyl 4-oxospiro[chromane-2,4′-piperidine]-1′-carboxylate (105 g, 70%) as a light yellow solid. ESI-MS m/z calc. 317.2. found 318.2 (M+1)+; Retention time: 1.78 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.87 (dd, J=7.8, 1.5 Hz, 1H), 7.55-7.45 (m, 1H), 7.10-6.90 (m, 2H), 3.95-3.80 (m, 2H), 3.26-3.17 (m, 2H), 2.72 (s, 2H), 2.03 (d, J=13.0 Hz, 2H), 1.68-1.58 (m, 2H), 1.46 (s, 9H).

Workup

  1. customMethanol was removed under reduced pressure
  2. dissolutionThe resulting residue was dissolved in ethyl acetate (150 mL)
  3. washwashed with 1M aqueous HCl (1×150 mL) and brine (2×100 mL)
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto afford a yellow oil
  8. temperaturewas heated at 60° C. until in solution
  9. dissolutionOnce dissolved
  10. temperatureto cool to 25° C
  11. filtrationCrystals were collected via vacuum filtration
  12. washrinsed with hexane

Sources & evidence

ORD record
ord-edd9468a14ab47eda7ea9a9c1889073a
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

Loading…