9H-fluoren-9-ylmethyl ({[(1S*,2R*,4R*)-1-(2-fluorophenyl)-2-(hydroxymethyl)-4-methoxycyclopentyl]amino}carbonothioyl)carbamate → [(4aR*,6S*,7aS*)-7a-(2-fluorophenyl)-6-methoxy-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-2-yl]amine

HRID 1842198Notes

Reaction equation

HRID 1842198 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]1([NH:17][C:18]([NH:20]C(=O)OCC2C3C=CC=CC=3C3C2=CC=CC=3)=[S:19])[CH2:12][C@H:11]([O:13][CH3:14])[CH2:10][C@H:9]1[CH2:15]O>CO>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C@:8]12[CH2:12][C@@H:11]([O:13][CH3:14])[CH2:10][C@H:9]1[CH2:15][S:19][C:18]([NH2:20])=[N:17]2

Participants

3

Reactant 1

HCID 578275719H-fluoren-9-ylmethyl ({[(1S*,2R*,4R*)-1-(2-fluorophenyl)-2-(hydroxymethyl)-4-methoxycyclopentyl]amino}carbonothioyl)carbamate

Product 1

HCID 57827676[(4aR*,6S*,7aS*)-7a-(2-fluorophenyl)-6-methoxy-4,4a,5,6,7,7a-hexahydrocyclopenta[d][1,3]thiazin-2-yl]amineYield 71%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 9H-fluoren-9-ylmethyl ({[(1S*,2R*,4R*)-1-(2-fluorophenyl)-2-(hydroxymethyl)-4-methoxycyclopentyl]amino}carbonothioyl)carbamate (340 mg) in methanol (20 mL)-concentrated hydrochloric acid (1 mL) was heated under reflux for three hours. The reaction solution was concentrated under reduced pressure. Acetonitrile (10 mL) and piperidine (2 mL) were added to the residue at room temperature, and the mixture was stirred at room temperature for one hour. The reaction solution was concentrated under reduced pressure. The crude product was purified by NH-silica gel column chromatography to obtain the title compound (130 mg).

Workup

  1. temperatureunder reflux for three hours
  2. concentrationThe reaction solution was concentrated under reduced pressure
  3. additionAcetonitrile (10 mL) and piperidine (2 mL) were added to the residue at room temperature
  4. concentrationThe reaction solution was concentrated under reduced pressure
  5. customThe crude product was purified by NH-silica gel column chromatography

Sources & evidence

ORD record
ord-ebcdd0a3bcb2422088f4af53c29b34de
Source dataset
uspto-grants-2015_02
Patent number
US08946210B2

Reaction notes

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