Proton sponge → HCID 86647718, compound

HRID 576113Notes

Reaction equation

HRID 576113 reaction equation
[F:1][C:2]([F:27])([F:26])[S:3]([O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH2:12][N:13](C)[CH2:14]2)=[CH:9][CH:8]=1)(=[O:5])=[O:4].CN(C)C1C2C(=CC=CC=2N(C)C)C=CC=1.ClC(OC(Cl)C)=O>ClCCCl>[F:26][C:2]([F:1])([F:27])[S:3]([O:6][C:7]1[CH:16]=[C:15]2[C:10]([CH:11]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[C:20]([Cl:25])[CH:19]=3)[CH2:12][NH:13][CH2:14]2)=[CH:9][CH:8]=1)(=[O:4])=[O:5]

Participants

5

Reactant 3

HCID 88675Proton spongeHCID 5213051-Chloroethyl chloroformateHCID 59580334HCID 59580334, compound

Product 1

HCID 86647718HCID 86647718, compoundYield 46.4%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To an ice-cold solution of 4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl trifluoromethanesulfonate (1.0 g, 2.3 mmol) and N1,N1,N8,N8-tetramethylnaphthalene-1,8-diamine (493 mg, 2.3 mmol) in 1,2-dichloroethane (25 mL) was added 1-chlorethyl chloroformate (0.75 mL, 6.9 mmol) drop wise. The mixture was heated to reflux for 1 hour. The mixture was cooled to room temperature, concentrated, and filtered through a pad of silica gel (1:1:1 hexanes/ethyl acetate/dichloromethane). The filtrate was concentrated, the residue dissolved in methanol (50 mL), and then heated to reflux for 1 hour. The mixture was cooled, concentrated, neutralized with aqueous saturated sodium bicarbonate and ethyl acetate, and then purified by column chromatography (hexanes to ethyl acetate) to give 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydroisoquinolin-7-yl trifluoromethanesulfonate (455 mg, 46%) as a brown oil: ESI MS m/z 426 [M+H]+.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 1 hour
  3. concentrationconcentrated
  4. filtrationfiltered through a pad of silica gel (1:1:1 hexanes/ethyl acetate/dichloromethane)
  5. concentrationThe filtrate was concentrated
  6. dissolutionthe residue dissolved in methanol (50 mL)
  7. temperatureheated
  8. temperatureto reflux for 1 hour
  9. temperatureThe mixture was cooled
  10. concentrationconcentrated
  11. custompurified by column chromatography (hexanes to ethyl acetate)

Sources & evidence

ORD record
ord-d0455a90b2ac4f2faf779e7577c79a2a
Source dataset
uspto-grants-2015_05
Patent number
US09034899B2

Reaction notes

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