Acetonitrile → 3-Cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester

HRID 857064Notes

Reaction equation

HRID 857064 reaction equation
[CH3:1][O:2][C:3]([CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7](=[O:14])[CH2:6]1)=[O:4].[CH3:15][Si:16](C#N)([CH3:18])[CH3:17].[C:21](#[N:23])C>C1(C)C=CC=CC=1.C(=O)(O)[O-].[Na+].[I-].[Zn+2].[I-]>[CH3:1][O:2][C:3]([CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:7]([C:21]#[N:23])([O:14][Si:16]([CH3:18])([CH3:17])[CH3:15])[CH2:6]1)=[O:4]

Participants

7

Reactant 3

HCID 6342AcetonitrileHCID 82115Trimethylsilyl cyanideHCID 2753058Methyl 3-oxo-2,3-dihydro-1H-indene-1-carboxylate

Product 1

HCID 114491283-Cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl esterYield 97%

Reagents, catalysts & solvents 3

HCID 9883512zinc(II)iodideCatalystHCID 1140TolueneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 3.80 g of 3-oxo-indan-1-carboxylic acid methyl ester (20.0 mmol, 1 equivalent) in 6 mL of toluene and 2 mL of acetonitrile was added 192 mg of zinc iodide (0.600 mmol, 0.03 equivalent) followed by 3.47 mL of trimethylsilyl cyanide (26.0 mmol, 1.3 equivalent). The reaction mixture was heated to 50° C. for 5 hours. The reaction mixture was then cooled to room temperature and diluted with 12 mL of toluene and 8 mL of a saturated aqueous sodium bicarbonate solution. After stirring the mixture for 1 hour the layers were separated. The organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution followed by 8 mL of a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and concentrated in vacuo to give 3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester as an oil (5.61 g, 97%). The silylated cyanohydrin title compound was obtained as a mixture of two diastereomers in a 2:1 ratio: 1H NMR (400 MHz, CDCl3): (major isomer) δ 7.54–7.50 (m, 1H), 7.42–7.38 (m, 3H), 4.14 (t, J=7.7 Hz, 1H), 3.78 (s, 3H), 3.01 (dd, J=13.3, 7.5 Hz, 1H), 2.79 (dd, J=13.3, 7.5 Hz, 1H), 0.26 (s, 9H); (minor isomer) 67.59–7.55 (m, 1H), 7.48–7.44 (m, 3H), 4.29 (t, J=7.5 Hz, 1H), 3.78 (s, 3H), 3.03 (dd, J=13.7, 7.5 Hz, 1H), 2.70 (dd, J=13.7, 7.5 Hz, 1H), 0.14 (s, 9H); 13C NMR (100 MHz, CDCl3): (unassigned) δ 172.3, 172.0, 142.3, 142.1, 140.1, 138.8, 130.8, 130.5, 129.1, 128.9, 125.8, 125.6, 124.7, 124.3, 120.8, 120.6, 75.4, 75.3, 52.7, 52.7, 47.4, 46.8, 45.6, 45.3, 1.4, 1.3; IR (neat, cm−1): 2956, 1739, 1477, 1436, 1253, 1197, 1169, 1135, 1092, 1033, 1011, 880, 843, 756, 623; Anal. Calcd for C15H19NO3Si: C, 62.25; H, 6.62; N, 4.84; Found: C, 62.20; H, 6.53; N, 4.92.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. customwere separated
  3. washThe organic layer was washed with another 8 mL of a saturated aqueous sodium bicarbonate solution
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-b22a144ec0df460a8f1af7bf869749b7
Source dataset
uspto-grants-2006_12
Patent number
US07144882B2

Reaction notes

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