Methyl chloroformate → HCID 71145253, compound

HRID 535317Notes

Reaction equation

HRID 535317 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[C:17]3[C:12](=[CH:13][C:14]([O:22][CH3:23])=[C:15]([O:18][CH:19]([CH3:21])[CH3:20])[CH:16]=3)[CH2:11][C:10](=[O:24])[N:9]2[C:25]2[CH:30]=[CH:29][C:28]([C:31]3([OH:35])[CH2:34][NH:33][CH2:32]3)=[CH:27][CH:26]=2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Cl[C:46]([O:48][CH3:49])=[O:47]>C(Cl)Cl.C([O-])(O)=O.[Na+]>[CH3:49][O:48][C:46]([N:33]1[CH2:34][C:31]([C:28]2[CH:29]=[CH:30][C:25]([N:9]3[C:10](=[O:24])[CH2:11][C:12]4[C:17](=[CH:16][C:15]([O:18][CH:19]([CH3:20])[CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=4)[C@@H:8]3[C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)=[CH:26][CH:27]=2)([OH:35])[CH2:32]1)=[O:47]

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 71145730HCID 71145730, compound

Product 1

HCID 71145253HCID 71145253, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of (S)-1-(4-chloro-phenyl)-2-[4-(3-hydroxy-azetidin-3-yl)-phenyl]-7-isopropoxy-6-methoxy-1,4-dihydro-2H-isoquinolin-3-one (example 56) (40 mg, 0.081 mmol) in DCM (2 ml) was immersed in an ice-bath. DIPEA (Fluka) (0.043 ml, 0.243 mmol) was added, followed by methyl chloroformate (Fluka) (8.17 μl, 0.105 mmol). Afterwards the reaction was stirred in an ice-bath for 30 min. The reaction mixture was taken up in aqueous NaHCO3 solution. The organic phase was extracted two times with DCM. The organic layers were pooled, dried over Na2SO4, filtered and concentrated in vacuo to obtain the crude product which was purified by preparative. TLC (DCM/MeOH 9:1; Rf range from 0.31 to 0.46 was scratched from the plate). The silicagel was taken up in 20 ml DCM/MeOH 1:1. The silicagel was filtered off. The filtrate was evaporated in vacuo to obtain the title compound as white solid.

Workup

  1. extractionThe organic phase was extracted two times with DCM
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto obtain the crude product which
  6. customwas purified by preparative
  7. filtrationThe silicagel was filtered off
  8. customThe filtrate was evaporated in vacuo

Sources & evidence

ORD record
ord-4f288834cbe24033bda01cc1a408b660
Source dataset
uspto-grants-2014_10
Patent number
US08859535B2

Reaction notes

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