Tert-butyl 3-oxopiperidine-1-carboxylate → HCID 66786630, compound

HRID 1096674Notes

Reaction equation

HRID 1096674 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]=[CH:7]1.[O:15]=[C:16]1[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1>>[OH:15][C:16]1([C:7]2[N:6]([CH2:5][CH2:4][CH2:3][O:2][CH3:1])[C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=3[N:8]=2)[CH2:21][CH2:20][CH2:19][N:18]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:17]1

Participants

3

Reactant 2

HCID 2756825Tert-butyl 3-oxopiperidine-1-carboxylateHCID 45590701HCID 45590701, compound

Product 1

HCID 66786630HCID 66786630, compound

Conditions

Temperature
-78 °C

Procedure

1-(3-methoxypropyl)-1H-benzo[d]imidazole (137A) (9.62 mmoles; 1.83 g) was added to an oven dried 250 mL round-bottomed flask equipped with an addition funnel and for stirring under nitrogen. Et2O (75 mL) was added and the solution was cooled to −78° C. with an acetone/CO2(s) bath. N-BuLi (2.5M in hexanes, 10.1 mmoles, 4.0 mL) was added drop-wise via syringe and the resultant solution was allowed to stir at −78° C. for 45 minutes. Tert-butyl 3-oxopiperidine-1-carboxylate (10.1 mmoles, 2.01 g) in END (25 mL) was then added drop-wise to the reaction solution at −78° C. via addition funnel and allowed to stir for 1 hr. The reaction solution was then allowed to warm to rt and stir for ihr. The reaction solution was then poured into ice-water, extracted with ethyl acetate, and washed once with saturated aqueous sodium chloride. The organic layer was collected and subsequently dried with anhydrous Na.2SO4 and filtered. The filtrate was collected, concentrated, and dried in-vacuo. The residue was then partially purified by chromatography on silica gel (5-15% CH3OH/CH2Cl2) to afford tert-butyl 3-hydroxy-3-(1-(3-methoxypropyl)-1H-benzo[d]imidazol-2-yl)piperidine-1-carboxylate (137E) as a mixture of products that was carried onto the next step without further purification. ESI-MS: m/z 390.4 (M+H)+.

Workup

  1. customdried 250 mL round-bottomed flask
  2. customequipped with an addition funnel
  3. additionEt2O (75 mL) was added
  4. stirringto stir at −78° C. for 45 minutes
  5. additionvia addition funnel
  6. stirringto stir for 1 hr
  7. temperatureto warm to rt
  8. stirringstir for ihr
  9. extractionextracted with ethyl acetate
  10. washwashed once with saturated aqueous sodium chloride
  11. customThe organic layer was collected
  12. customsubsequently dried with anhydrous Na
  13. filtration2SO4 and filtered
  14. customThe filtrate was collected
  15. concentrationconcentrated
  16. customdried in-vacuo
  17. customThe residue was then partially purified by chromatography on silica gel (5-15% CH3OH/CH2Cl2)

Sources & evidence

ORD record
ord-c76c7ee71199417db6e056398cb0a11b
Source dataset
uspto-grants-2012_03
Patent number
US08138168B1

Reaction notes

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