Acetyl chloride → 1-(Spiro[indoline-3,4'-piperidin]-1-yl)ethanone

HRID 849553Notes

Reaction equation

HRID 849553 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].C(OC([N:15]1[CH2:20][CH2:19][C:18]2([C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[NH:22][CH2:21]2)[CH2:17][CH2:16]1)=O)C1C=CC=CC=1.CCN(CC)CC>C(Cl)Cl>[C:1]([N:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:18]2([CH2:19][CH2:20][NH:15][CH2:16][CH2:17]2)[CH2:21]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 8471TriethylamineHCID 10914256Benzyl 1,2-dihydrospiro[indole-3,4'-piperidine]-1'-carboxylate

Product 1

HCID 217029651-(Spiro[indoline-3,4'-piperidin]-1-yl)ethanoneYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Acetyl chloride (1.4 mL, 19.9 mmol) was added to a solution of 5.35 g (16.6 mmol) of 1'-benzyloxycarbonyl-spiro(indoline-3,4'-piperidine) in 33 mL of CH2Cl2 and 3.2 mL (23.2 mmol) of Et3N keeping the temperature between 0-5° C. by cooling in ice bath. After 10 min the cold bath was removed and reaction was stirred for 30 min at which time a TLC indicated complete reaction. The solution was diluted with CH2Cl2 and washed with water, brine and dried over Na2SO4. The filtrate was concentrated to a thick oil and the oil was dissolved in 40 mL of EtOH. Acetic acid (3 mL) and 0.8 g of 10% Pd/C were added to the solution and the resulting mixture was hydrogenated on a Parr apparatus for 3 h. The catalyst was filtered and washed with EtOAc and the combined filtrate was concentrated. The residue was partitioned between CH2Cl2 and water and 2N NaOH was added to this mixture until the aqueous layer was basic. The layers were separated and the aqueous layer was extracted with CH2Cl2. The combined organic layer was washed with brine, dried over Na2SO4 and the filtrate was concentrated to give 2.93 g (77%) of the title compound sufficiently pure for use in the next reaction.

Workup

  1. temperatureby cooling in ice bath
  2. customAfter 10 min the cold bath was removed
  3. customreaction
  4. customreaction
  5. washwashed with water, brine
  6. dry with materialdried over Na2SO4
  7. concentrationThe filtrate was concentrated to a thick oil
  8. dissolutionthe oil was dissolved in 40 mL of EtOH
  9. additionAcetic acid (3 mL) and 0.8 g of 10% Pd/C were added to the solution
  10. waitthe resulting mixture was hydrogenated on a Parr apparatus for 3 h
  11. filtrationThe catalyst was filtered
  12. washwashed with EtOAc
  13. concentrationthe combined filtrate was concentrated
  14. customThe residue was partitioned between CH2Cl2 and water and 2N NaOH
  15. additionwas added to this mixture until the aqueous layer
  16. customThe layers were separated
  17. extractionthe aqueous layer was extracted with CH2Cl2
  18. washThe combined organic layer was washed with brine
  19. dry with materialdried over Na2SO4
  20. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-560e6b1b49bf40fb989e71fb7a137a1b
Source dataset
uspto-grants-2000_01
Patent number
US06013652

Reaction notes

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