Triethylamine → HCID 76568160, compound

HRID 1728118Notes

Reaction equation

HRID 1728118 reaction equation
Br[C:2]1[C:3]([F:36])=[C:4]([CH:12]2[C:17]3([C:25]4[C:20](=[CH:21][C:22]([Cl:26])=[CH:23][CH:24]=4)[NH:19][C:18]3=[O:27])[CH:16]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=3)[CH2:15][C:14](=[O:35])[NH:13]2)[C:5]([O:8][CH2:9][CH2:10][OH:11])=[CH:6][CH:7]=1.[C:37]([Si:39]([CH3:42])([CH3:41])[CH3:40])#[CH:38].C(N(CC)CC)C>CN(C)C=O.O>[Cl:26][C:22]1[CH:21]=[C:20]2[NH:19][C:18](=[O:27])[C:17]3([CH:16]([C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=4)[CH2:15][C:14](=[O:35])[NH:13][CH:12]3[C:4]3[C:5]([O:8][CH2:9][CH2:10][OH:11])=[CH:6][CH:7]=[C:2]([C:38]#[C:37][Si:39]([CH3:42])([CH3:41])[CH3:40])[C:3]=3[F:36])[C:25]2=[CH:24][CH:23]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 66111TrimethylsilylacetyleneHCID 76568123HCID 76568123, compound

Product 1

HCID 76568160HCID 76568160, compoundYield 40.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of racemic (2′R,3R,4′S)-2′-[3-bromo-2-fluoro-6-(2-hydroxy-ethoxy)-phenyl]-6-chloro-4′-(3-chlorophenyl)spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione (0.12 g, 0.202 mmol) prepared in example 183d in N,N-dimethyl formamide (1 mL) was added ethynyl-trimethyl-silane (0.28 mL, 2.0 mmol) (Aldrich) and triethylamine (0.127 g, 2.0 mmol). After the reaction mixture was degassed for 5 min, dichloro-bis-(triphenyl-phosphine) (14 mg, 0.02 mmol) (Strem) was added and the reaction mixture was heated at 100° C. under nitrogen for overnight. The reaction mixture was cooled to room temperature and diluted with water, extracted with ethyl acetate. The organic layers were combined, washed with water, brine, dried over MgSO4, filtered and concentrated. The residue was purified with chromatography to give racemic (2′R,3R,4′S)-6-chloro-4′-(3-chlorophenyl)-2′-[2-fluoro-6-(2-hydroxy-ethoxy)-3-trimethylsilanylethynyl-phenyl]spiro[3H-indole-3,3′-piperidine]-2,6′(1H)-dione as brown solid (Yield: 50 mg, 40.6%).

Workup

  1. customAfter the reaction mixture was degassed for 5 min
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with ethyl acetate
  4. washwashed with water, brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified with chromatography

Sources & evidence

ORD record
ord-960f0a34680b4c8e9cf943474668c9cd
Source dataset
uspto-grants-2009_02
Patent number
US07495007B2

Reaction notes

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