Isobutyl chloroformate → Tert-butyl 5-(2-(4-fluorophenyl)-6-(hydroxymethyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate

HRID 927276Notes

Reaction equation

HRID 927276 reaction equation
ClC(OCC(C)C)=O.[C:9]([O:13][C:14](=[O:40])[CH2:15][CH2:16][CH2:17][CH2:18][C:19]1[N:20]([C:33]2[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=2)[C:21](=[O:32])[C:22]2[C:27]([CH:28]=1)=[CH:26][C:25]([C:29](O)=[O:30])=[CH:24][CH:23]=2)([CH3:12])([CH3:11])[CH3:10].CCN(C(C)C)C(C)C.[BH4-].[Na+]>ClCCl.CO>[F:39][C:36]1[CH:37]=[CH:38][C:33]([N:20]2[C:19]([CH2:18][CH2:17][CH2:16][CH2:15][C:14]([O:13][C:9]([CH3:10])([CH3:12])[CH3:11])=[O:40])=[CH:28][C:27]3[C:22](=[CH:23][CH:24]=[C:25]([CH2:29][OH:30])[CH:26]=3)[C:21]2=[O:32])=[CH:34][CH:35]=1

Participants

7

Reactant 4

HCID 62365Isobutyl chloroformateHCID 81531DiisopropylethylamineHCID 4311764Sodium borohydrideHCID 900944973-(5-(Tert-butoxy)-5-oxopentyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxylic acid

Product 1

HCID 118558138Tert-butyl 5-(2-(4-fluorophenyl)-6-(hydroxymethyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoateYield 84%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Isobutyl chloroformate (0.285 mL, 2.184 mmol) was added to a stirred, 0° C. mixture of 3-(5-(tert-butoxy)-5-oxopentyl)-2-(4-fluorophenyl)-1-oxo-1,2-dihydroisoquinoline-6-carboxylic acid (800 mg, 1.820 mmol) and Hunig's Base (0.636 mL, 3.64 mmol) in Dichloromethane (20 mL) and the mixture was stirred at 0° C. for 3 h. The mixture was concentrated under reduced pressure with bath temp at 20° C., the residue was taken up in Dichloromethane (20 mL), NaBH4 (138 mg, 3.64 mmol) was added, the mixture was stirred at room temperature for 16 h. MeOH (10 mL) was added, and the resultant mixture was kept stirring at room temperature for 1 h. The mixture was diluted with dichloromethane (60 mL), washed with aqueous sodium hydrogen carbonate (saturated, 1×10 mL), dried (MgSO4), filtered and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with EtOAc/isohexane=1:1 to give tert-butyl 5-(2-(4-fluorophenyl)-6-(hydroxymethyl)-1-oxo-1,2-dihydroisoquinolin-3-yl)pentanoate (650 mg, 1.528 mmol) as a white solid.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure with bath temp at 20° C.
  2. stirringthe mixture was stirred at room temperature for 16 h
  3. washwashed with aqueous sodium hydrogen carbonate (saturated, 1×10 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by column chromatography on silica gel
  8. washeluting with EtOAc/isohexane=1:1

Sources & evidence

ORD record
ord-062d3510ffcf45d79b8f76a64d6129f2
Source dataset
uspto-grants-2016_03
Patent number
US09290454B2

Reaction notes

Loading…