Dichloromethane → n-{[(7s)-3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-3-(7,8-dimethoxy-1,2,4,5-tetrahydro-3h-3-benzazepin-3-yl)-n-methyl-4-oxobutan-1-amine hydrochloride

HRID 657565Notes

Reaction equation

HRID 657565 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:8](=[CH:9][C:10]=1[O:11][CH3:12])[C@@H:7]([CH2:13][NH:14][CH3:15])[CH2:6]2.[CH3:16][O:17][C:18]1[C:19]([O:35][CH3:36])=[CH:20][C:21]2NC[CH:25](C(=O)CCC=O)[CH2:24][CH2:23][C:22]=2[CH:34]=1.C(O[BH-](O[C:47](=[O:49])[CH3:48])OC(=O)C)(=O)C.[Na+].[OH-].[Na+].[Cl:53]CCl>>[ClH:53].[CH3:16][O:17][C:18]1[CH:34]=[C:22]2[C:21](=[CH:20][C:19]=1[O:35][CH3:36])[C@@H:24]([CH2:25][N:14]([CH3:15])[CH2:13][CH2:7][CH:48]([N:14]1[CH2:15][CH2:6][C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:10]([O:11][CH3:12])=[CH:9][C:8]=3[CH2:7][CH2:13]1)[CH:47]=[O:49])[CH2:23]2

Participants

6

Reactant 5

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 11499437(S)-1-(3,4-Dimethoxybicyclo(4.2.0)octa-1,3,5-trien-7-yl)-N-methylmethanamineHCID 876403464-(7,8-Dimethoxy-1,2,4,5-tetrahydro-3H-3-benzazepin-yl)-4-oxobutanal

Product 1

HCID 87640330n-{[(7s)-3,4-Dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}-3-(7,8-dimethoxy-1,2,4,5-tetrahydro-3h-3-benzazepin-3-yl)-n-methyl-4-oxobutan-1-amine hydrochloride

Procedure

At ambient temperature, 2.53 g (12.2 mmol) of {[(7S)-3,4-dimethoxybicyclo[4.2.0]octa-1,3,5-trien-7-yl]methyl}methylamine and 3.95 g (12.2 mmol/1 eq.) of the compound of Step 2 are mixed into 90 mL of dichloromethane. There are then added 3.88 g (18.3 mmol/1.5 eq.) of sodium triacetoxyborohydride and stirring is carried out at ambient temperature for 4 hours. There are then added 60 mL of 1N aqueous sodium hydroxide solution, followed by extraction twice with 150 mL of ethyl acetate. The combined organic phases are washed with 100 mL of water and then with 100 mL of saturated aqueous sodium chloride solution and are then dried over magnesium sulphate. After filtration and concentration, the residue is chromatographed over 300 g of silica (eluant:dichloromethane/ethanol/ammonia: 97/3/0.3) to yield the desired product in the form of the base. The latter is dissolved in 13 mL of isopropanol, converted into a salt using 0.67 mL of 4.8N ethanolic HCl and then recrystallised from 25 mL of ethyl acetate to yield the expected product.

Workup

  1. extractionfollowed by extraction twice with 150 mL of ethyl acetate
  2. washThe combined organic phases are washed with 100 mL of water
  3. dry with materialwith 100 mL of saturated aqueous sodium chloride solution and are then dried over magnesium sulphate
  4. filtrationAfter filtration and concentration
  5. customthe residue is chromatographed over 300 g of silica (eluant:dichloromethane/ethanol/ammonia: 97/3/0.3)

Sources & evidence

ORD record
ord-0887c5600aaa4085a7423204714fd254
Source dataset
uspto-grants-2011_12
Patent number
US08076325B2

Reaction notes

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