Red-Al → (R)-tert-butyl 2-(1'-benzylspiro[indoline-3,4'-piperidine]-4-yl)pyrrolidine-1-carboxylate

HRID 2190074Notes

Reaction equation

HRID 2190074 reaction equation
COCCO[AlH2-]OCCOC.[Na+].[CH2:13]([N:20]1[CH2:25][CH2:24][C:23]2([C:33]3[C:28](=[CH:29][CH:30]=[CH:31][C:32]=3[C@H:34]3[CH2:38][CH2:37][CH2:36][N:35]3[C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[NH:27][C:26]2=O)[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>C1(C)C=CC=CC=1>[CH2:13]([N:20]1[CH2:25][CH2:24][C:23]2([C:33]3[C:28](=[CH:29][CH:30]=[CH:31][C:32]=3[C@H:34]3[CH2:38][CH2:37][CH2:36][N:35]3[C:39]([O:41][C:42]([CH3:45])([CH3:44])[CH3:43])=[O:40])[NH:27][CH2:26]2)[CH2:22][CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

4

Reactant 2

HCID 16684438Red-AlHCID 68736950(R)-tert-butyl 2-(1'-benzyl-2-oxospiro[indoline-3,4'-piperidine]-4-yl)pyrrolidine-1-carboxylate

Product 1

HCID 68760890(R)-tert-butyl 2-(1'-benzylspiro[indoline-3,4'-piperidine]-4-yl)pyrrolidine-1-carboxylateYield 43%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

RED-AL (250 μL, 0.83 mmol) was added into a solution of (R)-tert-butyl 2-(1′-benzyl-2-oxospiro[indoline-3,4′-piperidine]-4-yl)pyrrolidine-1-carboxylate (120 mg, 0.26 mmol) in toluene (3 mL), and the resulting solution was heated to 70° C. for 30 minutes. The reaction was quenched by adding EtOAc (5 mL) into the reaction mixture. The resulting mixture was treated with 1M aqueous potassium sodium tartrate (2 mL) and was extracted with EtOAc (10 mL). The organic layer was washed with brine, dried with Na2SO4, filtered and concentrated. The residue was purified with flash chromatography to afford the product (R)-tert-butyl 2-(1′-benzylspiro[indoline-3,4′-piperidine]-4-yl)pyrrolidine-1-carboxylate (50 mg, 43.0%) as a solid. 1H NMR (CDCl3, 400 MHz) δ 7.30-7.40 (m, 4H), 7.18-7.20 (m, 1H), 6.90-7.00 (m, 1H), 6.42-6.52 (m, 1H), 5.20-5.40 (m, 1H), 3.40-3.80 (m, 4H), 3.18-3.40 (m, 1H), 2.80-3.00 (m, 2H), 2.22-2.42 (m, 3H), 2.20 (s, 2H), 1.95-2.02 (m, 2H), 1.70-1.85 (m, 2H), 1.56 (s, 4H), 1.38-1.42 (m, 1H), 1.22-1.30 (m, 1H), 1.20 (s, 6H). MS (APCI+) [M+H]+ 448.

Workup

  1. customThe reaction was quenched
  2. additionby adding EtOAc (5 mL) into the reaction mixture
  3. additionThe resulting mixture was treated with 1M aqueous potassium sodium tartrate (2 mL)
  4. extractionwas extracted with EtOAc (10 mL)
  5. washThe organic layer was washed with brine
  6. dry with materialdried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified with flash chromatography

Sources & evidence

ORD record
ord-a5d82c00b41949d3a8fa42a6fe05dedd
Source dataset
uspto-grants-2012_12
Patent number
US08324221B2

Reaction notes

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