Hydrogen Bromide → {(R)-1-[2-fluoro-4-(6-hydroxy-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-pyrrolidin-3-yl}-methyl-carbamic acid tert-butyl ester

HRID 69431Notes

Reaction equation

HRID 69431 reaction equation
[C:1]([O:5][C:6](=[O:34])[N:7]([C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:29][CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[C:25]([O:30]C)[CH:26]=4)[C:21]3=[O:32])=[CH:16][C:15]=2[F:33])[CH2:10]1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].Br.C(=O)([O-])O.[Na+].CC(OC(OC(OC(C)(C)C)=O)=O)(C)C>O1CCOCC1.O>[C:1]([O:5][C:6](=[O:34])[N:7]([C@@H:9]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:29][CH2:28][C:27]4[C:22](=[CH:23][CH:24]=[C:25]([OH:30])[CH:26]=4)[C:21]3=[O:32])=[CH:16][C:15]=2[F:33])[CH2:10]1)[CH3:8])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 260Hydrogen BromideHCID 90495Di-tert-butyl dicarbonateHCID 516892Sodium BicarbonateHCID 68989909{(R)-1-[2-fluoro-4-(6-methoxy-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-pyrrolidin-3-yl}-methyl-carbamic acid tert-butyl ester

Product 1

HCID 68991872{(R)-1-[2-fluoro-4-(6-hydroxy-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-pyrrolidin-3-yl}-methyl-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

According to Method L, {(R)-1-[2-fluoro-4-(6-methoxy-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-phenyl]-pyrrolidin-3-yl}-methyl-carbamic acid tert-butyl ester was treated with hydrogen bromide. The raw product (5.5 g) was dissolved in 1,4-dioxan (50 mL) and water (50 mL), sodium hydrogencarbonate (2.6 g) and lastly Boc2O (3.38 g) were added. After 3 hours the 1,4-dioxan was removed in the rotary evaporator and the residue was distributed between water and ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. In this way the product was obtained with molecular weight 455.53 (C25H30FN3O4); MS (ESI): 456 (M+H+).

Workup

  1. customAfter 3 hours the 1,4-dioxan was removed in the rotary evaporator
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. concentrationconcentrated
  4. customIn this way the product was obtained with molecular weight 455.53 (C25H30FN3O4)

Sources & evidence

ORD record
ord-acb4ebd49b784df997b58c5fd71106eb
Source dataset
uspto-grants-2014_09
Patent number
US08822495B2

Reaction notes

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