Potassium Sodium Tartrate → HCID 59536305, compound

HRID 445381Notes

Reaction equation

HRID 445381 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:8])=[N:6][CH:7]=1.C([Mg]Cl)(C)C.[CH:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH2:17][CH2:16][N:15]=1.Cl[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1COCC1>[Cl:8][C:5]1[N:6]=[CH:7][C:2]([CH:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:17][CH2:16][N:15]2[C:25]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[O:26])=[CH:3][CH:4]=1

Participants

7

Reactant 5

HCID 9357Potassium Sodium TartrateHCID 10387Benzyl chloroformateHCID 767053,4-DihydroisoquinolineHCID 27344145-Bromo-2-chloropyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 59536305HCID 59536305, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a pear-shaped flask was added 5-bromo-2-chloropyridine (440 mg, 2286 μmol), dry THF (10 mL), and an ice bath. After stirring for 5 min, a 2M solution of isopropylmagnesium chloride (1.15 mL, 2300 μmol) was added. The solution was allowed to stir in the ice bath for 2 h, then transferred to a solution of 3,4-dihydroisoquinoline (165 mg, 1258 μmol), dry THF (5 mL), and benzyl chloroformate (0.20 mL, 1350 μmol) that had been stirring in an ice bath for 15 min. The solution was allowed to warm to RT. After 1 h, LC-MS indicated only partial conversion. Another 2 eq of the Grignard were prepared as described above and added to the reaction. After a further 15 h, LC-MS shows no further progress. The reaction was poured into sat'd Rochelle's salt and extracted with EtOAc (3×20 mL). The combined organics were washed with brine and concentrated in vacuo and adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (12 g), eluting with 0% to 20% EtOAc in hexanes, to provide crude benzyl 1-(6-chloropyridin-3-yl)-3,4-dihydro-isoquinoline-2(1H)-carboxylate as a yellow oil. The crude oil was carried into the next step.

Workup

  1. stirringhad been stirring in an ice bath for 15 min
  2. waitAfter 1 h
  3. customAnother 2 eq of the Grignard were prepared
  4. additionadded to the reaction
  5. waitAfter a further 15 h
  6. extractionextracted with EtOAc (3×20 mL)
  7. washThe combined organics were washed with brine
  8. concentrationconcentrated in vacuo
  9. customchromatographed through a Redi-Sep® pre-packed silica gel column (12 g)
  10. washeluting with 0% to 20% EtOAc in hexanes

Sources & evidence

ORD record
ord-dbdb595e2c7d4bea92fbd0a4e9705308
Source dataset
uspto-grants-2013_07
Patent number
US08476297B2

Reaction notes

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