Potassium Sodium Tartrate → Spiro[cyclobutane-1,3'-indoline]

HRID 736978Notes

Reaction equation

HRID 736978 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].F[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1([C:20]#[N:21])[CH2:19][CH2:18]OC[CH2:15]1.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C(COC)OC>[NH:21]1[C:8]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:14]2([CH2:15][CH2:18][CH2:19]2)[CH2:20]1

Participants

5

Reactant 3

HCID 9357Potassium Sodium TartrateHCID 21226445Aluminium lithium hydrideHCID 49875771HCID 49875771, compound

Product 1

HCID 27274706Spiro[cyclobutane-1,3'-indoline]Yield 10.2%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

Add LiAlH4 (266 mg, 7.01 mmol) to a solution of 4-(2-fluoro-phenyl)-tetrahydro-pyran-4-carbonitrile (488 mg, 2.72 mmol) in dimethoxyethane (30 mL). Stir the solution at reflux for 4d, then add aq. Satd Rochelle's salt solution (30 mL) and stir for an additional 1 h at RT. Extract the mixture with Et2O (3×30 mL). Combine the organic extracts and wash with brine (30 mL). Dry, filter and concentrate the organic solution then purify the crude material by flash chromatography, using a linear gradient of 100% hexanes to 30% EtOAc/hexanes, to give the title compound (44 mg, 10%) as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.31 (m, 1H), 7.03 (dt, 1H, J=1.4, 7.5), 6.79 (dt, 1H, J=0.9, 7.5), 6.64 (d, 1H, J=7.9), 2.36 (m, 2H), 2.21 (m, 2H), 2.02 (m, 2H).

Workup

  1. extractionExtract the mixture with Et2O (3×30 mL)
  2. washCombine the organic extracts and wash with brine (30 mL)
  3. customDry
  4. filtrationfilter
  5. concentrationconcentrate the organic solution
  6. customthen purify the crude material by flash chromatography

Sources & evidence

ORD record
ord-18f89183ce0141799af9704149dc9492
Source dataset
uspto-grants-2009_09
Patent number
US07595339B2

Reaction notes

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