Potassium bis(trimethylsilyl)amide → (S)-3-Vinyl-3,4-dihydro-1H-isoquinoline-2-carboxylic Acid Tert-butyl Ester

HRID 660661Notes

Reaction equation

HRID 660661 reaction equation
[CH3:1][Si]([N-][Si](C)(C)C)(C)C.[K+].[C:11]([O:15][C:16]([N:18]1[C@H:27]([CH:28]=O)[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[C:11]([O:15][C:16]([N:18]1[C@H:27]([CH:28]=[CH2:1])[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12]

Participants

5

Reactant 2

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 22861260(S)-tert-Butyl 3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 68838676(S)-3-Vinyl-3,4-dihydro-1H-isoquinoline-2-carboxylic Acid Tert-butyl Ester

Reagents, catalysts & solvents 2

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyltriphenylphosphonium bromide (2.07 g, 5.8 mmol) in THF (20 mL) at −78° C. is added KHMDS (11.0 mL, 5.5 mmol) and the mixture is stirred for 1.5 h. A solution of (S)-3-formyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (0.94 g, 3.6 mmol) in THF (10 mL) is added and the solution stirred at −78-C for 1.5 h before warming to RT. The reaction is quenched with water (10 mL) and extracted with EtOAc (2×30 mL). The organic extracts are washed with 1N HCl (3×35 mL), brine (2×30 mL) and dried over Na2SO4. Purification by flash chromatography using a gradient of 0-15% EtOAc/hexane affords the title compound.

Workup

  1. stirringthe solution stirred at −78-C for 1.5 h
  2. customThe reaction is quenched with water (10 mL)
  3. extractionextracted with EtOAc (2×30 mL)
  4. washThe organic extracts are washed with 1N HCl (3×35 mL), brine (2×30 mL)
  5. dry with materialdried over Na2SO4
  6. customPurification by flash chromatography

Sources & evidence

ORD record
ord-60f5df8fe4294b20a5e9b54781c9bcba
Source dataset
uspto-grants-2011_12
Patent number
US08084448B2

Reaction notes

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