Water → racemic (2'R,3R,4'S)-4'-(3-chlorophenyl)-6-cyclopropyl-2'-isopropenylspiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dione

HRID 1728186Notes

Reaction equation

HRID 1728186 reaction equation
Br[C:2]1[CH:7]=[C:6]2[NH:8][C:9](=[O:27])[C:10]3([CH:15]([C:16]4[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=4)[CH2:14][C:13](=[O:23])[NH:12][CH:11]3[C:24]([CH3:26])=[CH2:25])[C:5]2=[CH:4][CH:3]=1.O.[CH:29]1(B(O)O)[CH2:31][CH2:30]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:22][C:18]1[CH:17]=[C:16]([CH:15]2[CH2:14][C:13](=[O:23])[NH:12][CH:11]([C:24]([CH3:26])=[CH2:25])[C:10]32[C:5]2[C:6](=[CH:7][C:2]([CH:29]4[CH2:31][CH2:30]4)=[CH:3][CH:4]=2)[NH:8][C:9]3=[O:27])[CH:21]=[CH:20][CH:19]=1

Participants

7

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 76568131HCID 76568131, compound

Product 1

HCID 76568182racemic (2'R,3R,4'S)-4'-(3-chlorophenyl)-6-cyclopropyl-2'-isopropenylspiro[3H-indole-3,3'-piperidine]-2,6'(1H)-dioneYield 17.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

Under nitrogen atmosphere, to a solution of racemic (2′R,3R,4′S)-6-bromo-4′-(3-chlorophenyl)-2′-isopropenyl-2,6′-dioxospiro[indole-3,3′-piperidine]-1-carboxyl acid tert-butyl ester (0.050 g) prepared in Example 172b in toluene (5 mL) was added water (0.1 mL), cyclopropyl boronic acid (0.020 g, 0.23 mmol), K3PO4 (0.098 g, 0.46 mmol), and Pd(PPh3)4 (0.018 g, 0.016 mmol). The mixture was irradiated at 130° C. by microwave for 0.5 h. Then cooled to room temperature and filtered through a short pad of silica gel, the silica gel was washed with ethyl acetate. The filtrate was concentrated. To the residue was added trifluoroacetic acid (5 mL). The solution was stirred at room temperature for 0.5 h, then partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with NaHCO3 aqueous solution, dried over MgSO4 and concentrated. The residue was purified with Prep.LC to give title compound as a white solid (Yield: 8 mg).

Workup

  1. customThe mixture was irradiated at 130° C. by microwave for 0.5 h
  2. filtrationfiltered through a short pad of silica gel
  3. washthe silica gel was washed with ethyl acetate
  4. concentrationThe filtrate was concentrated
  5. additionTo the residue was added trifluoroacetic acid (5 mL)
  6. custompartitioned between ethyl acetate and water
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with ethyl acetate
  9. washThe combined organic layer was washed with NaHCO3 aqueous solution
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customThe residue was purified with Prep.LC

Sources & evidence

ORD record
ord-cc6785bb26e345338ea0bcaa01031e38
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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