Methyl 3-(aminomethyl)-2,3-dihydro-1H-indene-1-carboxylate → 1,3,4,5-Tetrahydro-2H-1,5-methano-3-benzazepin-2-one

HRID 10083Notes

Reaction equation

HRID 10083 reaction equation
C[O:2][C:3]([CH:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]([CH2:14][NH2:15])[CH2:6]1)=O.CC(C)([O-])C.[Na+]>CO>[O:2]=[C:3]1[NH:15][CH2:14][CH:7]2[CH2:6][CH:5]1[C:13]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=12

Participants

4

Reactant 2

HCID 11206516Methyl 3-(aminomethyl)-2,3-dihydro-1H-indene-1-carboxylateHCID 23676156Sodium t-butoxide

Product 1

HCID 101301841,3,4,5-Tetrahydro-2H-1,5-methano-3-benzazepin-2-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-aminomethyl-indan-1-carboxylic acid methyl ester (assume 20.0 mmol, 1 equivalent) in 50 mL of methanol was added 3.84 g of sodium tert-butoxide (40.0 mmol, 2.0 equivalent). The reaction mixture was heated to a reflux for 2 hours. The reaction was cooled to room temperature and concentrated in vacuo. The residue was partitioned between 60 mL of ethyl acetate and 40 mL of 5% aqueous solution of sodium bicarbonate. The aqueous layer was extracted twice more with 50 mL of ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated to provide a solid material. Recrystallization of the solid from 10 mL of toluene provided white crystals of the title compound (1.78 g, 51%). mp=172–173° C.; 1H NMR (400 MHz, CDCl3): δ 7.33 (d, J=7.6 Hz, 1H), 7.31 (d, J=7.6 Hz, 1H), 7.22 (t, J=7.6 Hz, 1H), 7.18 (t, J=7.6 Hz, 1H), 5.62 (s, 1H), 3.68 (dd, J=11.2, 4.1 Hz, 1H), 3.55 (d, J=3.7 Hz, 1H), 3.43–3.37 (m, 1H), 3.18 (d, J=11.2 Hz, 1H), 2.52–2.45 (m, 1H), 2.32 (d, J=11.2 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ 173.6, 144.7, 144.6, 128.0, 127.7, 123.2, 122.9, 49.3, 47.9, 39.1, 38.4; IR (neat, cm−1): 3218, 2949, 2872, 1666, 1485, 1459, 1400, 1328, 1303, 1288, 1250, 1215, 1122, 1104, 1045, 1004, 946, 910, 756, 730, 643, 613; Anal. Calcd for C11H121NO: C, 76.28; H, 6.40; N, 8.09; Found: C, 75.94; H, 6.27; N, 7.99.

Workup

  1. temperatureThe reaction mixture was heated to
  2. temperaturea reflux for 2 hours
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between 60 mL of ethyl acetate and 40 mL of 5% aqueous solution of sodium bicarbonate
  5. extractionThe aqueous layer was extracted twice more with 50 mL of ethyl acetate
  6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customto provide a solid material
  9. customRecrystallization of the solid from 10 mL of toluene provided white crystals of the title compound (1.78 g, 51%)

Sources & evidence

ORD record
ord-fe9d2c6d13af48da90b699d1f3a1186e
Source dataset
uspto-grants-2006_08
Patent number
US07091372B2

Reaction notes

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