2,4-Dimethoxybenzylamine → (3R)-tert-Butyl 3-((2,4-dimethoxybenzylamino)methyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 1159090Notes

Reaction equation

HRID 1159090 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH:15]([C@H:17]1[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][N:18]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=O.[CH3:34][O:35][C:36]1[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[CH:40][C:37]=1[CH2:38][NH2:39]>CO.C(Cl)Cl>[CH3:34][O:35][C:36]1[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[CH:40][C:37]=1[CH2:38][NH:39][CH2:15][C@H:17]1[CH2:26][C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH2:19][N:18]1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28]

Participants

5

Reactant 3

HCID 5972502,4-DimethoxybenzylamineHCID 5049666Sodium triacetoxyborohydrideHCID 57350014(R)-Tert-butyl 3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 68688148(3R)-tert-Butyl 3-((2,4-dimethoxybenzylamino)methyl)-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

Sodium triacetoxyborohydride (3.1 g, 15 mm) was added to a mixture of (3R)-tert-butyl 3-formyl-3,4-dihydroisoquinoline-2(1H)-carboxylate (1.3 g, 5.0 mmol theory), 2,4-dimethoxybenzylamine (0.77 ml, 5.5 mmol), and dry 4 A sieves in 1,2-dichloroethane (25 ml) stirring at ambient temperature. After stirring at ambient temperature overnight the reaction solution was transferred to a separatory funnel with EtOAc and saturated NaHCO3. Extraction with EtOAc (2×), washing the combined organic layers with brine and drying over MgSO4 afforded 1.6 g of crude product. Flash chromatography (SiO2, 1 to 10% 2N N3 in MeOH/CH2Cl2) gave pure product (1.3 g, 63% yield over the previous 3 steps). MS (ESI) 413 (M+H).

Workup

  1. dry with materialdry 4 A sieves in 1,2-dichloroethane (25 ml)
  2. stirringAfter stirring at ambient temperature overnight the reaction solution
  3. customwas transferred to a separatory funnel with EtOAc and saturated NaHCO3
  4. extractionExtraction with EtOAc (2×)
  5. washwashing the combined organic layers with brine
  6. dry with materialdrying over MgSO4
  7. customafforded 1.6 g of crude product

Sources & evidence

ORD record
ord-d0fe821ba3be46729fa6d53bd8047390
Source dataset
uspto-grants-2010_10
Patent number
US07812024B2

Reaction notes

Loading…