Sodium hydride → HCID 10134015, compound

HRID 2250130Notes

Reaction equation

HRID 2250130 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([OH:18])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[CH2:22][CH2:23][CH2:24][N:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:18][CH2:22][CH2:23][CH2:24][N:25]3[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]3)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79625Piperidine, 1-(3-chloropropyl)-HCID 10060623tert-Butyl 6-hydroxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 10134015HCID 10134015, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a round-bottom flask, equipped with stir bar and septum, is placed 6-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1 g, 4.01 mmol), KI (599 mg, 4.01 mmol) and NaH (162 mg, 95% dry, 6.42 mmol). Then, dry DMF (20 mL, 0.5 M) is added via syringe followed by N-(3-chloropropyl)piperidine (0.85 mL, 5.2 mmol). The reaction is allowed to stir at 70 degrees overnight. In the morning, the reaction is quenched with water, extracted into EtOAc (3×20 mL) and dried over brine. Column chromatography in 9:1 DCM:MeOH affords 6-(3-piperidin-1-yl-propoxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester an orange oil (1 g, 67%). Mass sec hit M+1, 375; LCMS>95% @230 nm and ELSD. In a similar manner the Examples 35, 139, and 164 are prepared:

Workup

  1. customTo a round-bottom flask, equipped
  2. stirringto stir at 70 degrees overnight
  3. customIn the morning, the reaction is quenched with water
  4. extractionextracted into EtOAc (3×20 mL)
  5. dry with materialdried over brine

Sources & evidence

ORD record
ord-2a900d20ae02404f8a1ec4e98e0fa6b6
Source dataset
uspto-grants-2008_01
Patent number
US07314937B2

Reaction notes

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