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 1842082Notes

Reaction equation

HRID 1842082 reaction equation
C1C2C(COC(=O)[NH:17][C:18]([NH:20][C@@:21]3([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[F:36])[CH2:25][C@@H:24]([O:26][CH3:27])[CH2:23][C@H:22]3[CH2:28]O)=[S:19])C3C(=CC=CC=3)C=2C=CC=1>CO>[F:36][C:31]1[CH:32]=[CH:33][CH:34]=[CH:35][C:30]=1[C@:21]12[CH2:25][C@@H:24]([O:26][CH3:27])[CH2:23][C@H:22]1[CH2:28][S:19][C:18]([NH2:17])=[N:20]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-7d34bd6002b149f997d89abef8247d99
Source dataset
uspto-grants-2015_02
Patent number
US08946211B2

Reaction notes

Loading…