Tetrahydrofuran → (S)-N-tert-butyloxycarbonyl-3-(-Methyl-thiocarbamoyloxymethyl)-1,2,3,4tetrahydroisoquinoline

HRID 618690Notes

Reaction equation

HRID 618690 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:17]([CH2:18][OH:19])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].C[N:23]=[C:24]=[S:25].O1CCC[CH2:27]1>[Cl-].[Na+].O>[C:1]([O:5][C:6]([N:8]1[C@H:17]([CH:18]([CH3:27])[O:19][C:24](=[S:25])[NH2:23])[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 11167Methyl isothiocyanateHCID 24758Sodium hydrideHCID 53811416tert-butyl (3S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Product 1

HCID 88311676(S)-N-tert-butyloxycarbonyl-3-(-Methyl-thiocarbamoyloxymethyl)-1,2,3,4tetrahydroisoquinolineYield 81.8%

Reagents, catalysts & solvents 1

HCID 57417360Sodium chloride; waterSolvent

Procedure

To 50 mL dichloromethane solution containing (S)-3-hydroxymethy-1,2,3,4-tetrahydroisoquinoline (4.53 g, 27.75 mmol) was added di-tert-butyl dicarbonate (5.45 g, 25.0 mmol, 0.9 eq) and the reaction mixture was stirred for 2 hours until no gas bubbling was observed. The reaction mixture was washed with 0.5 N HCl (50 mL) followed by brine (50 mL) to remove the residual starting material. After drying wth MgSO4 and filtration the, dichloromethane mixture was evaporated to yield crude (S)-N-tert-Butyloxycarbonyl-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline. The crude N-tert-Butyloxycarbonyl-3-hydroxymethyl-1,2,3,4-tetrahydroisoquinoline was redissolved in 100 mL tetrahydrofuran. NaH (60%, 1.22 g) was added portion by portion to the solution at 0° C. and after 30 min stirring at room temperature, MeNCS (2.23 g) was added and the mixture was stirred for 2 h at rt. Brine (50 mL) was added to the mixture to quench the reaction and after evaporation of volatile component in vacuo, it was extracted with dichloromethane (50 mL×2) and combined layer was dried (MgSO4), filtered, evaporated. The resulting material was chromatographed with hexane-EtOAc (4:1) mixture over SiO2 to provide 7.07 g (81.8%) of (S)-N-tert-butyloxycarbonyl-3-(-Methyl-thiocarbamoyloxymethyl)-1,2,3,4tetrahydroisoquinoline. This material was dissolved in THF(30 mL) and 10 mL conc. HCl was added to the solution. One hour later, 5 mL of conc. HCl was added and stirred another 1 h until the reaction was finished. The reaction mixture was diluted with 30 mL of water and volatile components were evaporated. During the evaporation, desired product was precipitated as white solid. The solid was filtered and dried to yield the product as the hydrochloride salt (4.8 g).

Workup

  1. stirringthe mixture was stirred for 2 h at rt
  2. customto quench
  3. customthe reaction
  4. customafter evaporation of volatile component in vacuo, it
  5. extractionwas extracted with dichloromethane (50 mL×2)
  6. dry with materialwas dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe resulting material was chromatographed with hexane-EtOAc (4:1) mixture over SiO2

Sources & evidence

ORD record
ord-a0bf1a977551460da72faffda621ed15
Source dataset
uspto-grants-1999_09
Patent number
US05955471

Reaction notes

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