p-Toluenesulfonic acid monohydrate → Methyl 3-(aminomethyl)-2,3-dihydro-1H-indene-1-carboxylate

HRID 1271362Notes

Reaction equation

HRID 1271362 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]([C:19]#[N:20])(O[Si](C)(C)C)[CH2:6]1)=[O:4].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[H][H]>CO.[OH-].[OH-].[Pd+2]>[CH3:1][O:2][C:3]([CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]([CH2:19][NH2:20])[CH2:6]1)=[O:4]

Participants

6

Reactant 3

HCID 521998p-Toluenesulfonic acid monohydrateHCID 114491283-Cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 11206516Methyl 3-(aminomethyl)-2,3-dihydro-1H-indene-1-carboxylateYield 89%

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolvent

Procedure

To a solution of 5.79 g of 3-cyano-3-trimethylsilanyloxy-indan-1-carboxylic acid methyl ester (20.0 mmol, 1.0 equivalent) in 25 mL of methanol was added 5.71 g of p-toluenesulfonic acid monohydrate (30.0 mmol, 1.5 equivalent). The solution was stirred for 15 minutes and then 4.21 g of 20% palladium hydroxide on carbon, 50% wet by weight, (3.00 mmol, 0.15 equivalent) was added. The reaction mixture was subjected to hydrogenolysis at 50 psi of hydrogen over 24 hours. After this time, the reaction mixture was filtered through Celite and typically used-filtrate in the next step (Example 60D). The isolation of the title compound was conducted as follows: the filtrate was concentrated in vacuo; the residue was partitioned between 30 mL of methylene chloride and 20 mL of a saturated aqueous solution of sodium carbonate; the aqueous layer was extracted with 15 mL of methylene chloride; the combined aqueous layers were washed with 40 mL of a saturated aqueous solution of sodium chloride; the organic solution was dried over anhydrous sodium sulfate and concentrated to afford the title compound as an oil (3.65 g, 89%) with approximately a 10:1 ratio of diastereomers; (major diastereomer) 1H NMR (400 MHz, CDCl3): δ 7.43 (dd, J=6.9, 1.6 Hz, 1H), 7.29–7.25 (m, 3H), 4.09 (t, J=8.1 Hz, 1H), 3.80 (s, 3H), 3.31–3.24 (m, 1H), 3.14 (dd, J=12.8, 4.7 Hz, 1H), 2.98 (dd, J=12.8, 7.3 Hz,1H), 2.62–2.52 (m, 1H), 2.31–2.42 (m, 1H), 1.3 (bs, 2H).

Workup

  1. filtrationAfter this time, the reaction mixture was filtered through Celite and typically used-filtrate in the next step (Example 60D)
  2. concentrationthe filtrate was concentrated in vacuo
  3. customthe residue was partitioned between 30 mL of methylene chloride and 20 mL of a saturated aqueous solution of sodium carbonate
  4. extractionthe aqueous layer was extracted with 15 mL of methylene chloride
  5. washthe combined aqueous layers were washed with 40 mL of a saturated aqueous solution of sodium chloride
  6. dry with materialthe organic solution was dried over anhydrous sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-11a1544d6ac94672934944d213c14a8e
Source dataset
uspto-grants-2007_04
Patent number
US07205300B2

Reaction notes

Loading…