Hydrochloric Acid → Racemic (4aSR,7aSR)-7a-(5-Bromo-2-fluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine

HRID 2060754Notes

Reaction equation

HRID 2060754 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[CH:5][C:6]([F:27])=[C:7]([C:9]23[CH2:17][O:16][CH2:15][CH:14]2[CH2:13][S:12][C:11]([NH:18]C(=O)C2C=CC=CC=2)=[N:10]3)[CH:8]=1>>[Br:2][C:3]1[CH:4]=[CH:5][C:6]([F:27])=[C:7]([C:9]23[CH2:17][O:16][CH2:15][CH:14]2[CH2:13][S:12][C:11]([NH2:18])=[N:10]3)[CH:8]=1

Participants

3

Reactant 2

HCID 313Hydrochloric AcidHCID 57504886N-(7a-(5-bromo-2-fluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide

Product 1

HCID 66847566Racemic (4aSR,7aSR)-7a-(5-Bromo-2-fluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amineYield 85.3%

Conditions

Temperature
90 °C

Procedure

5 N Aqueous hydrochloric acid (158 mL) is added to N-(7a-(5-bromo-2-fluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-yl)benzamide (16.35 g, 7.89 mmol) and the mixture is heated to 90° C. After 18 hours, the mixture is allowed to cool to ambient temperature and washed with dichloromethane. The organic layer is extracted once with 5 N aqueous hydrochloric acid. The pH of the aqueous layer is adjusted to basic with 50% aqueous sodium hydroxide and is extracted twice with 10% isopropyl alcohol:dichloromethane. The organic layer is concentrated under reduced pressure. The resulting residue is purified by radial chromatography eluting with 2% to 5% 7 N ammonia in methanol:dichloromethane to give the title compound (2.23 g, 47%). ES/MS m/e (79Br/81Br) 331, 333 (M+1).

Workup

  1. temperatureto cool to ambient temperature
  2. washwashed with dichloromethane
  3. extractionThe organic layer is extracted once with 5 N aqueous hydrochloric acid
  4. extractionis extracted twice with 10% isopropyl alcohol
  5. concentrationThe organic layer is concentrated under reduced pressure
  6. customThe resulting residue is purified by radial chromatography
  7. washeluting with 2% to 5% 7 N ammonia in methanol

Sources & evidence

ORD record
ord-3832ced28e0c439e882f4323f4f0da26
Source dataset
uspto-grants-2012_10
Patent number
US08278441B2

Reaction notes

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