Cesium carbonate → 2,5-anhydro-3-deoxy-4-O-(5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-O-(4-nitrobenzoyl)-L-threo-pentitol

HRID 577494Notes

Reaction equation

HRID 577494 reaction equation
[N+:1]([C:4]1[CH:23]=[CH:22][C:7]([C:8]([O:10][CH2:11][C@H:12]2[CH2:16][C@H:15]([O:17]S(C)(=O)=O)[CH2:14][O:13]2)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].[Cl:24][C:25]1[CH:34]=[C:33](O)[C:32]([Cl:36])=[C:31]2[C:26]=1[CH2:27][CH2:28][NH:29][C:30]2=[O:37].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O.C(OCC)(=O)C>[Cl:24][C:25]1[CH:34]=[C:33]([O:17][C@H:15]2[CH2:14][O:13][C@@H:12]([CH2:11][O:10][C:8](=[O:9])[C:7]3[CH:22]=[CH:23][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=3)[CH2:16]2)[C:32]([Cl:36])=[C:31]2[C:26]=1[CH2:27][CH2:28][NH:29][C:30]2=[O:37]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 867237185,8-dichloro-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-oneHCID 86723720((2R,4S)-4-((methylsulfonyl)oxy)tetrahydrofuran-2-yl)methyl 4-nitrobenzoate

Product 1

HCID 867237192,5-anhydro-3-deoxy-4-O-(5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-O-(4-nitrobenzoyl)-L-threo-pentitolYield 31%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of ((2R,4S)-4-((methylsulfonyl)oxy)tetrahydrofuran-2-yl)methyl 4-nitrobenzoate (296m, 300 mg, 0.869 mmol), 5,8-dichloro-7-hydroxy-3,4-dihydroisoquinolin-1(2H)-one (296 g, 222 mg, 0.956 mmol), and cesium carbonate (566 mg, 1.74 mmol) in N,N-dimethylformamide (8 mL) was heated to 100° C. for three hours. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate (50 mL), washed with water (2×50 mL) and brine (50 mL), dried over sodium sulfate, concentrated to dryness, and purified by silica gel chromatography (eluting with a gradient of 0-100% ethyl acetate in heptane) to give 2,5-anhydro-3-deoxy-4-O-(5,8-dichloro-1-oxo-1,2,3,4-tetrahydroisoquinolin-7-yl)-1-O-(4-nitrobenzoyl)-L-threo-pentitol (296n, 128 mg, 31% yield) as a solid. 1H NMR (400 MHz, CDCl3) δ 8.18-8.33 (m, 4H), 7.03 (s, 1H), 6.09 (br. s., 1H), 4.99 (td, J=4.28, 1.96 Hz, 1H), 4.56-4.62 (m, 2H), 4.42-4.52 (m, 1H), 4.27 (d, J=10.64 Hz, 1H), 4.02 (dd, J=10.58, 4.34 Hz, 1H), 3.48 (td, J=6.36, 3.91 Hz, 2H), 2.99-3.09 (m, 2H), 2.56 (ddd, J=14.24, 8.19, 6.42 Hz, 1H), 2.18 (dd, J=14.12, 5.07 Hz, 1H). MS: 481 [M+1]

Workup

  1. washwashed with water (2×50 mL) and brine (50 mL)
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated to dryness
  4. custompurified by silica gel chromatography (
  5. washeluting with a gradient of 0-100% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-a2685de888434f8bb0713280dfa0a0b0
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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