Benzoyl isothiocyanate → (4aR,6R,8aS)-6-benzyloxymethyl-8a-(2-fluorophenyl)-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-ylamine

HRID 217990Notes

Reaction equation

HRID 217990 reaction equation
C([N:9]=[C:10]=[S:11])(=O)C1C=CC=CC=1.[NH2:12][C@@:13]1([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[F:36])[CH2:18][O:17][C@@H:16]([CH2:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH2:15][C@H:14]1[CH2:28]O>ClCCl>[CH2:21]([O:20][CH2:19][C@@H:16]1[O:17][CH2:18][C@@:13]2([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=3[F:36])[C@H:14]([CH2:28][S:11][C:10]([NH2:9])=[N:12]2)[CH2:15]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

4

Reactant 2

HCID 68284Benzoyl isothiocyanateHCID 59281193[(2R,4R,5S)-5-amino-2-benzyloxymethyl-5-(2-fluorophenyl)tetrahydropyran-4-yl]methanol

Product 1

HCID 59281170(4aR,6R,8aS)-6-benzyloxymethyl-8a-(2-fluorophenyl)-4,4a,5,6,8,8a-hexahydro-7-oxa-3-thia-1-azanaphthalen-2-ylamine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Benzoyl isothiocyanate (893 μl) was added dropwise to a solution of [(2R,4R,5S)-5-amino-2-benzyloxymethyl-5-(2-fluorophenyl)tetrahydropyran-4-yl]methanol (2.08 g) in dichloromethane (30 ml). The reaction solution was stirred at room temperature for three hours, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography. Several drops of concentrated hydrochloric acid were added to a solution of the resulting intermediate in methanol (40 ml), and the mixture was heated under reflux for five hours. The reaction solution was returned to room temperature, and then the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (40 ml) and DBU (2 ml) was added, followed by heating under reflux for five hours. The solvent was evaporated under reduced pressure and the residue was purified by NH-silica gel column chromatography to obtain the title compound (1.61 g).

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customThe residue was purified by silica gel column chromatography
  3. additionSeveral drops of concentrated hydrochloric acid were added to a solution of the resulting intermediate in methanol (40 ml)
  4. temperaturethe mixture was heated
  5. temperatureunder reflux for five hours
  6. customwas returned to room temperature
  7. customthe solvent was evaporated under reduced pressure
  8. dissolutionThe residue was dissolved in methanol (40 ml)
  9. additionDBU (2 ml) was added
  10. temperatureby heating
  11. temperatureunder reflux for five hours
  12. customThe solvent was evaporated under reduced pressure
  13. customthe residue was purified by NH-silica gel column chromatography

Sources & evidence

ORD record
ord-f73f67fcd79844499934d858917deffc
Source dataset
uspto-grants-2012_06
Patent number
US08198269B2

Reaction notes

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