9H-fluoren-9-ylmethyl ({[(1S*,2R*,4S*)-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 1693162Notes

Reaction equation

HRID 1693162 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 578277249H-fluoren-9-ylmethyl ({[(1S*,2R*,4S*)-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 95.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 9H-fluoren-9-ylmethyl ({[(1S*,2R*,4S*)-1-(2-fluorophenyl)-2-(hydroxymethyl)-4-methoxycyclopentyl]amino}carbonothioyl)carbamate (330 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 (1 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 resulting crude product was purified by NH-silica gel column chromatography to obtain the title compound (170 mg).

Workup

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

Sources & evidence

ORD record
ord-5b1e4d948c0a4e4e8dc4cf8dd3cf2783
Source dataset
uspto-grants-2012_04
Patent number
US08158620B2

Reaction notes

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