Potassium Phosphate, Tribasic → HCID 76567969, compound

HRID 1728111Notes

Reaction equation

HRID 1728111 reaction equation
C(OC([N:8]1[C:32]2[C:27](=[CH:28][CH:29]=[C:30](Br)[CH:31]=2)[C:10]2([CH:15]([C:16]3[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=3)[CH2:14][C:13](=[O:23])[NH:12][CH:11]2[C:24]([CH3:26])=[CH2:25])[C:9]1=[O:34])=O)(C)(C)C.N1C2C(=CC=CC=2)[CH2:37][C:36]1=O.[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:27]2[C:32](=[CH:31][C:30]([C:36]#[CH:37])=[CH:29][CH:28]=2)[NH:8][C:9]3=[O:34])[CH:21]=[CH:20][CH:19]=1

Participants

5

Reactant 2

HCID 62657Potassium Phosphate, TribasicHCID 77580822HCID 77580822, compound

Product 1

HCID 76567969HCID 76567969, compoundYield 5.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of racemic (2′R,3R,4′S)-6-bromo-4′-(3-chlorophenyl)-2′-isopropenyl-2,6′-dioxospiro[indole-3,3′-piperidine]-1-carboxylic acid tert-butyl ester-1,3-dihydro-indole-2-one (54 mg, 0.1 mmol) prepared in example 173a, Pd(PPh3)4 (20 mg, 0.02 mmol), K3PO4 (110 mg, 0.5 mmol), dimethyl trimethylsilylethynylborate (1 mL, 0.5 M, 0.5 mmol) in toluene (3 mL) was heated under microwave irradiation at 130° C. for 1 hour. The solvent was removed in vacuo. To the residue was added methanol (3 mL) and aqueous NaOH (2 N, 3 mL). The mixture was stirred at room temperature for 2 h. The solvent was removed in vacuo, the residue was diluted with ethyl acetate (20 mL), washed with brine, saturated NH4Cl, brine, then organic layer was separated, and concentrated. The residue was purified by preparative HPLC to give racemic (2′R,3R,4′S)-4′-(3-chlorophenyl)-6-ethynyl-2′-isopropenylspiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (2 mg).

Workup

  1. customThe solvent was removed in vacuo
  2. additionTo the residue was added methanol (3 mL) and aqueous NaOH (2 N, 3 mL)
  3. customThe solvent was removed in vacuo
  4. additionthe residue was diluted with ethyl acetate (20 mL)
  5. washwashed with brine, saturated NH4Cl, brine
  6. customorganic layer was separated
  7. concentrationconcentrated
  8. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-df4331ca9af844299bd8ad4ea6dd5a64
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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