Acetic Acid → [4-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yloxy)-piperidin-1-yl]-acetic acid ethyl ester

HRID 2059583Notes

Reaction equation

HRID 2059583 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[CH:7][NH:8][C:9]2=[O:12])=[CH:4][C:3]=1[O:13][CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1.C(N(CC)CC)C.C(O)(=O)C.[CH2:31]([O:33][C:34](=[O:37])[CH:35]=O)[CH3:32].C([BH3-])#N.[Na+]>CO>[CH2:31]([O:33][C:34](=[O:37])[CH2:35][N:17]1[CH2:18][CH2:19][CH:14]([O:13][C:3]2[CH:4]=[C:5]3[C:10](=[CH:11][C:2]=2[Cl:1])[C:9](=[O:12])[NH:8][CH:7]=[CH:6]3)[CH2:15][CH2:16]1)[CH3:32]

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8471TriethylamineHCID 70211Ethyl oxoacetateHCID 5003444Sodium cyanoborohydrideHCID 576524487-Chloro-6-(piperidin-4-yloxy)isoquinolin-1(2H)-one

Product 1

HCID 59229774[4-(7-Chloro-1-oxo-1,2-dihydro-isoquinolin-6-yloxy)-piperidin-1-yl]-acetic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

1.5 g (5.38 mmol) of 7-Chloro-6-(piperidin-4-yloxy)-2H-isoquinolin-1-one (7, free base) were dissolved in 100 mL of methanol. At room temperature, 1.09 g (10.8 mmol) of triethylamine, 3.23 g (53.8 mmol) of acetic acid, 7.63 g (33.6 mmol) of glyoxylic acid ethyl ester and molecular sieves (4 A) were added, followed by 253.6 mg (4.04 mmol) of sodium cyanoborohydride. After stirring for 2 h at room temperature, the reaction mixture was filtered and the filtrate was evaporated i. vac. The residue was dissolved in dichloromethane and washed with 1 N NaOH and sat. NaCl-solution. The organic layer was dried with MgSO4 and evaporated. The obtained crude product was used without further purification.

Workup

  1. filtrationthe reaction mixture was filtered
  2. customthe filtrate was evaporated i
  3. dissolutionThe residue was dissolved in dichloromethane
  4. washwashed with 1 N NaOH and sat. NaCl-solution
  5. dry with materialThe organic layer was dried with MgSO4
  6. customevaporated
  7. customThe obtained crude product
  8. customwas used without further purification

Sources & evidence

ORD record
ord-602e338b992f49f89dbf5fc79ac323be
Source dataset
uspto-grants-2012_10
Patent number
US08278294B2

Reaction notes

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