4-Chlorophenyl Isocyanate → (3S)-2N-(4-chlorophenylaminocarbonyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

HRID 1432546Notes

Reaction equation

HRID 1432546 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH2:9][NH:8][CH:7]([C:15]([OH:17])=[O:16])[CH2:6]2.[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([N:25]=[C:26]=[O:27])=[CH:21][CH:20]=1>[OH-].[Na+].O1CCOCC1>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([NH:25][C:26]([N:8]2[C@H:7]([C:15]([OH:17])=[O:16])[CH2:6][C:5]3[C:10](=[CH:11][C:12]([O:13][CH3:14])=[C:3]([O:2][CH3:1])[CH:4]=3)[CH2:9]2)=[O:27])=[CH:21][CH:20]=1

Participants

5

Reactant 2

HCID 76934-Chlorophenyl Isocyanate2×HCID 31605726,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

Product 1

HCID 86606520(3S)-2N-(4-chlorophenylaminocarbonyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acidYield 157.3%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of (S) 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (1.00 g, 2.44 mmol) in 1N aq. NaOH (10 mL), a solution of 4-chlorophenylisocyanate (563 mg, 3.66 mmol) in dioxane (8 mL) was added. The mixture was stirred at room temperature overnight. More 4-chlorophenylisocyanate (600 mg, 3.91 mmol) in dioxane (5 mL) was added. It was stirred for another day. It was then washed with Et2O (2×). The aqueous layer was separated, acidified with 4N HCl to pH 1 to 2. The product was extracted with EtOAc. The EtOAc solution was dried over Na2SO4, concentrated in vacuo to give a solid (1.50 g), which was sufficiently pure to be used in the next reaction. MS 391.1 and 393.1 (M+H, Cl pattern).

Workup

  1. stirringIt was stirred for another day
  2. washIt was then washed with Et2O (2×)
  3. customThe aqueous layer was separated
  4. extractionThe product was extracted with EtOAc
  5. dry with materialThe EtOAc solution was dried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f41c5560bf2b455585584cc08fddffba
Source dataset
uspto-grants-2009_11
Patent number
US07612089B2

Reaction notes

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