Triethylamine → 1-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-1-propyl)-3-pyrrolidinacetic acid methyl ester

HRID 863559Notes

Reaction equation

HRID 863559 reaction equation
Cl.[CH:2]1[C:12]2[CH2:11][CH2:10][C:9]3[CH:13]=[CH:14][CH:15]=[CH:16][C:8]=3[N:7]([CH2:17][CH2:18][CH2:19][N:20]3[CH2:25][CH2:24][CH2:23][C@H:22]([C:26]([OH:28])=[O:27])[CH2:21]3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH2:29](N(CC)CC)C.CS(Cl)(=O)=O.COC(=O)CC1CCNC1>C1COCC1>[CH3:29][O:28][C:26](=[O:27])[CH2:22][CH:23]1[CH2:24][CH2:25][N:20]([CH2:19][CH2:18][CH2:17][N:7]2[C:8]3[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=3[CH2:10][CH2:11][C:12]3[CH:2]=[CH:3][CH:4]=[CH:5][C:6]2=3)[CH2:21]1

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 31297Methanesulfonyl chlorideHCID 13424175Methyl 2-(pyrrolidin-3-yl)acetateHCID 70302592(S)-1-(3-(10,11-Dihydro-5H-dibenzo[b,f]azepin-5-yl)-1-propyl)-3-piperidinecarboxylic acid hydrochloride

Product 1

HCID 536769941-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-1-propyl)-3-pyrrolidinacetic acid methyl esterYield 27%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-(10,11-Dihydro-5H-dibenzo[b,f]azepin-5-yl)-1-propanol (2.0 g, 0.0079 mol, prepared as described in example 10) was dissolved in dry THF (25 ml) under an atmosphere of nitrogen, and triethylamine (2.75 ml) was added. Methanesulfonyl chloride (0.61 ml, 0.0079 mol) was added dropwise and when addition was complete the reaction mixture was stirred for 45 minutes. The mixture was filtered and 3-pyrrolidinacetic acid methyl ester (2.4 g, 0.012 mol) was added to the filtrate. The mixture was heated at reflux temperature for 4 h and then stirred at room temperature for 48 h. Triethylamine (2.2 ml) was added and the mixture was heated at reflux temperature for 24 h. After cooling to room temperature the solvent was removed by evaporation in vacuo. The residue was purified by column chromatography on silica gel (125 g) using a mixture of dichloromethane and methanol (9:1) as eluent, affording 0.9 g (27%) of 1-(3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-1-propyl)-3-pyrrolidinacetic acid methyl ester as an oil. Rf : 0.15 (SiO2 ; dichloromethane/methanol/acetic acid=20:2:1).

Workup

  1. additionwhen addition
  2. filtrationThe mixture was filtered
  3. temperatureThe mixture was heated
  4. temperatureat reflux temperature for 4 h
  5. stirringstirred at room temperature for 48 h
  6. temperaturethe mixture was heated
  7. temperatureat reflux temperature for 24 h
  8. customwas removed by evaporation in vacuo
  9. customThe residue was purified by column chromatography on silica gel (125 g)
  10. additiona mixture of dichloromethane and methanol (9:1) as eluent

Sources & evidence

ORD record
ord-b834657aa7f8495b866db023e80e4510
Source dataset
uspto-grants-1998_02
Patent number
US05721254

Reaction notes

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