Benzyl Alcohol → [1-(tert-Butoxycarbonylamino-methyl)-6,7-dimethoxy-isoquinolin-4-yl]-carbamic acid benzyl ester

HRID 14664Notes

Reaction equation

HRID 14664 reaction equation
[C:1]([O:5][C:6](=[O:28])[NH:7][CH2:8][C:9]1[C:18]2[C:13](=[CH:14][C:15]([O:21][CH3:22])=[C:16]([O:19][CH3:20])[CH:17]=2)[C:12](C(N=[N+]=[N-])=O)=[CH:11][N:10]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:29]([OH:36])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([N:39]([CH2:42]C)CC)C.CC[O:46]C(C)=O>C1(C)C=CC=CC=1.[NH4+].[OH-]>[CH2:29]([O:36][C:42](=[O:46])[NH:39][C:12]1[C:13]2[C:18](=[CH:17][C:16]([O:19][CH3:20])=[C:15]([O:21][CH3:22])[CH:14]=2)[C:9]([CH2:8][NH:7][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:28])=[N:10][CH:11]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 59341108HCID 59341108, compound

Product 1

HCID 59341103[1-(tert-Butoxycarbonylamino-methyl)-6,7-dimethoxy-isoquinolin-4-yl]-carbamic acid benzyl esterYield 64%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 14923Ammonium HydroxideSolvent

Conditions

Temperature
80 °C

Procedure

A solution of (4-Azidocarbonyl-6,7-dimethoxy-isoquinolin-1-ylmethyl)-carbamic acid tert-butyl ester (1.36 g) in 40 mL of toluene was heated to 95° C. for 20 min, then the reaction flask was removed from the oil bath and benzyl alcohol (600 mg, 1.5 eq) and triethylamine (355 mg, 1.0 eq) were added. The reaction was allowed to stir at 80° C. After 3 h, TLC indicated clean conversion to a single product. The reaction was diluted with 30 mL EtOAc, and 25 mL 1% NH4OH. The aqueous phase was extracted with 20 mL EtOAc, and the combined organics were washed with brine, dried over MgSO4, and filtered though a 1-cm plug of silica. After removal of the solvent, the residue was purified by flash chromatography, eluting with a gradient of 1%-5% MeOH in DCM to give 1.05 g (64%) of the desired product. H1-NMR (CDCl3): δ 8.50 (br s, 1H), 7.3-7.5 (m, 1H), 6.75 (s, 1H), 6.12 (s, 1H), 5.24 (s, 2H), 4.82 (d, 1H), 4.00 (s, 3H), 3.91 (s, 3H), 1.49 (s, 9H).

Workup

  1. additionwere added
  2. extractionThe aqueous phase was extracted with 20 mL EtOAc
  3. washthe combined organics were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered though a 1-cm plug of silica
  6. customAfter removal of the solvent
  7. customthe residue was purified by flash chromatography
  8. washeluting with a gradient of 1%-5% MeOH in DCM

Sources & evidence

ORD record
ord-c03858224ddf4e1dbd68079510db102a
Source dataset
uspto-grants-2010_06
Patent number
US07732446B1

Reaction notes

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