Triethylamine → Benzyl 1'-methylspiro[indoline-3,4'-piperidine]-1-carboxylate

HRID 849552Notes

Reaction equation

HRID 849552 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][C:5]2([C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[NH:9][CH2:8]2)[CH2:4][CH2:3]1.CCN(CC)CC.Cl[C:24]([O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)=[O:25]>C(Cl)Cl>[CH2:27]([O:26][C:24]([N:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[C:5]2([CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]2)[CH2:8]1)=[O:25])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

5

Reactant 3

HCID 8471Triethylamine3×HCID 10387Benzyl chloroformate3×HCID 128015871'-Methylspiro[indoline-3,4'-piperidine]

Product 1

HCID 10711919Benzyl 1'-methylspiro[indoline-3,4'-piperidine]-1-carboxylateYield 71.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 99 g (489 mmol) of 1'-methylspiro(indoline-3,4'-piperidine) (prepared according to Ong, H. H. et al, J. Med. Chem., 1983, 26, 981-986) in 1 L of CH2Cl2 and 82 mL (539 mmol) of Et3N was cooled to 0-5° C. with an ice bath and 77 mL (539 mmol) of benzyl chloroformate was added over 30 min keeping the reaction temperature below 10° C. After stirring for 2 h 19 mL (136 mmol) of Et3N and 15 mL (105 mmol) of benzyl chloroformate were added since the reaction was incomplete and stirred for 2 h. At this time, additional 19 mL (136 mmol) of Et3N and 15 mL (105 mmol) of benzyl chloroformate were added. After 1 h, when a TLC indicated a complete reaction, the solution was concentrated in vacuo and the residue was partitioned between ether and saturated NaHCO3. The layers were separated, the organic layer was washed with saturated NaHCO3 and brine, and dried over MgSO4. The filtrate was concentrated and the residue was chromatographed on 2 kg of silica gel using 1-5% MeOH/CH2Cl2 to obtain 117 g (71%) of 1-benzyloxycarbonyl-1'-methylspiro(indoline-3,4'-piperidine) as a yellow oil.

Workup

  1. customthe reaction temperature below 10° C
  2. additionwere added since the reaction
  3. waitAfter 1 h
  4. customa complete reaction
  5. concentrationthe solution was concentrated in vacuo
  6. customthe residue was partitioned between ether and saturated NaHCO3
  7. customThe layers were separated
  8. washthe organic layer was washed with saturated NaHCO3 and brine
  9. dry with materialdried over MgSO4
  10. concentrationThe filtrate was concentrated
  11. customthe residue was chromatographed on 2 kg of silica gel using 1-5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-72ea82e1cff0456a8fa3714f912b84e4
Source dataset
uspto-grants-2000_01
Patent number
US06013652

Reaction notes

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