Water → HCID 76568006, compound

HRID 1728098Notes

Reaction equation

HRID 1728098 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32](Br)[CH:33]=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]2([CH2:27][CH3:28])[CH2:26][CH2:25]2)[C:9]1=[O:36])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:37]1(B(O)O)[CH2:39][CH2:38]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>O.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>[C:1]([O:5][C:6]([N:8]1[C:34]2[C:29](=[CH:30][CH:31]=[C:32]([CH:37]3[CH2:39][CH2:38]3)[CH:33]=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]2([CH2:27][CH3:28])[CH2:26][CH2:25]2)[C:9]1=[O:36])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 2760897Cyclopropylboronic acidHCID 76567867HCID 76567867, compound

Product 1

HCID 76568006HCID 76568006, compoundYield 38.1%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
130 °C

Procedure

Under Argon atmosphere, racemic (2′R,3R,4′S)-6-bromo-4′-(3-chlorophenyl)-2′-(1-ethyl-cyclopropyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-carboxylic acid tert-butyl ester (28 mg, 0.049 mmol), cyclopropylboronic acid (4.5 mg, 0.0524 mmol), Pd(PPh3)4 (5 mg), K3PO4 (50 mg) and a few drops of water were mixed in toluene (3 mL). The mixture was heated under microwave irradiation at 130° C. for 20 min. Then the solution was poured into water and the aqueous layer was extracted with EtOAc. The organic layer was dried and concentrated. The residue was purified by Prep-TLC to obtain racemic (2′R,3R,4′S)-6-cyclopropyl-4′-(3-chlorophenyl)-2′-(1-ethyl-cyclopropyl)-2,3-dihydro-2,6′-dioxospiro[indole-3,3′-piperidine]-1-carboxylic acid tert-butyl ester (10 mg).

Workup

  1. extractionthe aqueous layer was extracted with EtOAc
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customThe residue was purified by Prep-TLC

Sources & evidence

ORD record
ord-f57e32cbfc134bf88245fdf919715504
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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