Sodium Hydroxide → 2-({[(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)-3-oxopropyl]-amino)-ethanol hydrochloride

HRID 657573Notes

Reaction equation

HRID 657573 reaction equation
[ClH:1].[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C@@H:8]([CH2:14][NH:15][CH2:16][CH2:17][C:18]([N:20]1[CH2:26][CH2:25][C:24]3[CH:27]=[C:28]([O:33][CH3:34])[C:29]([O:31][CH3:32])=[CH:30][C:23]=3[CH2:22][CH2:21]1)=[O:19])[CH2:7]2.[O:35]1CC(O)O[CH2:37][CH:36]1O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C(Cl)Cl>[ClH:1].[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[C@@H:8]([CH2:14][N:15]([CH2:16][CH2:17][C:18]([N:20]1[CH2:21][CH2:22][C:23]3[CH:30]=[C:29]([O:31][CH3:32])[C:28]([O:33][CH3:34])=[CH:27][C:24]=3[CH2:25][CH2:26]1)=[O:19])[CH2:37][CH2:36][OH:35])[CH2:7]2

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 186078Glycolaldehyde dimerHCID 5049666Sodium triacetoxyborohydrideHCID 68974197N-{[(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)-3-oxopropan-1-amine hydrochloride

Product 1

HCID 689752592-({[(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)-3-oxopropyl]-amino)-ethanol hydrochloride

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1 g (2.2 mmol) of (7S)-N-[(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)-3-oxopropan-1-amine (obtained by returning the compound of Example 4 to the base), 0.4 g (3.3 mmol) of 1,4-dioxane-2,5-diol, 0.7 g (3.3 mmol) of sodium triacetoxyborohydride and 8 mL of methylene chloride are mixed together. After 45 minutes at ambient temperature, the reaction mixture is rendered basic with 10 mL of 1N sodium hydroxide solution and stirring is carried out for half an hour. The phases are separated, the aqueous phase is extracted twice with ethyl acetate, the organic phases are combined, washed with water and then with saturated NaCl solution and dried over MgSO4. After evaporating off the solvent, a residue is isolated which is chromatographed over silica (eluant: CH2Cl2/EtOH/NH4OH 95/5/0.5) to yield the expected compound, which is converted into its hydrochloride using 2N ethereal HCl solution.

Workup

  1. additionare mixed together
  2. waitis carried out for half an hour
  3. customThe phases are separated
  4. extractionthe aqueous phase is extracted twice with ethyl acetate
  5. washwashed with water
  6. dry with materialwith saturated NaCl solution and dried over MgSO4
  7. customAfter evaporating off the solvent
  8. customa residue is isolated which
  9. customis chromatographed over silica (eluant: CH2Cl2/EtOH/NH4OH 95/5/0.5)

Sources & evidence

ORD record
ord-0b431beba1614c86a27acf835d059d0a
Source dataset
uspto-grants-2011_12
Patent number
US08076325B2

Reaction notes

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