9-Fluorenylmethyl chloroformate → (S)-(9H-fluoren-9-yl)methyl 1-(2-(4-methoxybenzyl)-8-chloro-1-oxo-1,2-dihydroisoquinolin-3-yl)ethylcarbamate

HRID 518262Notes

Reaction equation

HRID 518262 reaction equation
[CH3:1][O:2][C:3]1[CH:24]=[CH:23][C:6]([CH2:7][N:8]2[C:17]([C@@H:18]([NH2:20])[CH3:19])=[CH:16][C:15]3[C:10](=[C:11]([Cl:21])[CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:22])=[CH:5][CH:4]=1.C([O-])(O)=O.[Na+].[C:30](Cl)([O:32][CH2:33][CH:34]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[C:40]2[C:35]1=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:31]>C(Cl)Cl.O>[CH3:1][O:2][C:3]1[CH:24]=[CH:23][C:6]([CH2:7][N:8]2[C:17]([C@@H:18]([NH:20][C:30](=[O:31])[O:32][CH2:33][CH:34]3[C:46]4[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=4[C:40]4[C:35]3=[CH:36][CH:37]=[CH:38][CH:39]=4)[CH3:19])=[CH:16][C:15]3[C:10](=[C:11]([Cl:21])[CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:22])=[CH:5][CH:4]=1

Participants

6

Reactant 3

HCID 343679-Fluorenylmethyl chloroformateHCID 516892Sodium BicarbonateHCID 66615532(S)-2-(4-methoxybenzyl)-3-(1-aminoethyl)-8-chloroisoquinolin-1 (2H)-one

Product 1

HCID 71232890(S)-(9H-fluoren-9-yl)methyl 1-(2-(4-methoxybenzyl)-8-chloro-1-oxo-1,2-dihydroisoquinolin-3-yl)ethylcarbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-2-(4-methoxybenzyl)-3-(1-aminoethyl)-8-chloroisoquinolin-1(2H)-one (343) (20 g, 58.3 mmol, 1.0 eq) and NaHCO3 (12.7 g, 291.51 mmol, 5.0 eq) in DCM (120 mL) and water (60 mL) at RT, Fmoc-Cl (15.7 g, 61.22 mmol, 1.05 eq) was slowly added and the resulting mixture was stirred at RT for 1 h. The reaction mixture was poured into water (200 mL) and extracted with DCM (3×100 mL). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo to afford (S)-(9H-fluoren-9-yl)methyl 1-(2-(4-methoxybenzyl)-8-chloro-1-oxo-1,2-dihydroisoquinolin-3-yl)ethylcarbamate (344).

Workup

  1. extractionextracted with DCM (3×100 mL)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-e35f1f080fac4dea9f9e392ac71affa9
Source dataset
uspto-grants-2015_08
Patent number
US09115141B2

Reaction notes

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