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 1693166Notes

Reaction equation

HRID 1693166 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-6843ec2050cc4d10bf8ed4c8013b936a
Source dataset
uspto-grants-2012_04
Patent number
US08158620B2

Reaction notes

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