Triethylamine → HCID 59731904, compound

HRID 132168Notes

Reaction equation

HRID 132168 reaction equation
C[O:2][C:3](=O)[CH:4]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][C:7]=1[CH2:20]O.CS(Cl)(=O)=O.[CH2:36]([N:38](CC)CC)C>ClCCl>[C:26]([O:25][C:23](=[O:24])[NH:22][CH:4]1[C:3](=[O:2])[N:38]([CH3:36])[CH2:20][C:7]2[CH:8]=[C:9]([O:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:10]=[CH:11][C:6]=2[CH2:5]1)([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 67317716HCID 67317716, compound

Product 1

HCID 59731904HCID 59731904, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-(2-acetoxymethyl-4-benzyloxy-phenyl)-2-tert-butoxycarbonylamino-propionic acid methyl ester (1.85 g, 4.0 mmol) in methanol (40 mL) was added potassium carbonate (560 mg, 4.0 mmol) at room temperature and stirred for 1 h. The reaction mixture was diluted with dichloromethane (150 mL), washed with 1.0 M aqueous hydrogen chloride and dried (Na2SO4) to give the pure 3-(4-benzyloxy-2-hydroxymethyl-phenyl)-2-tert-butoxycarbonylamino-propionic acid methyl ester in almost quantitative yield. To the alcohol (800 mg, 1.93 mmol) in dichloromethane (50 mL) was added methanesulfonyl chloride (0.18 mL, 2.3 mmol) followed by triethylamine (0.38 mL, 2.70 mmol) at 0° C. and then brought to room temperature. After 1 h, the reaction mixture was washed with aqueous sodium hydrogencarbonate, dried (Na2SO4). The solvent was removed, dissolved the crude product in anhydrous THF (20 mL) followed by addition of 2.0 M solution of methylamine in THF (10 mL) in a sealed tube. The sealed tube was heated at 80° C. for a period of 12 h and then removed the solvent. The crude product was purified by flash chromatography using 30% ethyl acetate in hexane to give (8-benzyloxy-2-methyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[c]azepin-4-yl)-carbamic acid tert-butyl ester in 39% overall yield. 1H NMR (500 MHz, CDCl3): in δ 7.40-7.31 (m, 5 H), 7.01-7.00 (m, 1 H), 6.83-6.82 (m, 1 H), 6.66 (s, 1 H), 5.91-5.90 (m, 1 H), 5.13-5.01 (m, 4 H), 3.50-3.46 (m, 1 H), 3.03 (s, 3 H), 2.85-2.78 (m, 1 H), 1.45 (s, 9 H).

Workup

  1. custombrought to room temperature
  2. washthe reaction mixture was washed with aqueous sodium hydrogencarbonate
  3. dry with materialdried (Na2SO4)
  4. customThe solvent was removed
  5. dissolutiondissolved the crude product in anhydrous THF (20 mL)
  6. additionfollowed by addition of 2.0 M solution of methylamine in THF (10 mL) in a sealed tube
  7. customremoved the solvent
  8. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-71f7ce6fdfce4ef3bfef06dacaf2d6d0
Source dataset
uspto-grants-2008_06
Patent number
US07384930B2

Reaction notes

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