Trifluoroacetic acid → 7-chloro-6-(4-methyl-thiazol-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

HRID 1670549Notes

Reaction equation

HRID 1670549 reaction equation
C(O)(C(F)(F)F)=O.C(OC([N:15]1[CH2:21][CH2:20][C:19]2[C:22]([CH2:27][S:28][C:29]3[S:30][CH:31]=[C:32]([CH3:34])[N:33]=3)=[C:23]([Cl:26])[CH:24]=[CH:25][C:18]=2[CH2:17][CH2:16]1)=O)(C)(C)C>C(Cl)Cl>[Cl:26][C:23]1[CH:24]=[CH:25][C:18]2[CH2:17][CH2:16][NH:15][CH2:21][CH2:20][C:19]=2[C:22]=1[CH2:27][S:28][C:29]1[S:30][CH:31]=[C:32]([CH3:34])[N:33]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 673358963-tert-butoxycarbonyl-7-chloro-6-(4-methyl-thiazol-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine

Product 1

HCID 598222817-chloro-6-(4-methyl-thiazol-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepineYield 99%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Add TFA (19 mL) to a solution of 3-tert-butoxycarbonyl-7-chloro-6-(4-methyl-thiazol-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.395 g, 0.93 mmol) in anhydrous DCM (19 mL) at room temperature and stir under nitrogen overnight. Concentrate the reaction mixture in vacuo and purify by SCX chromatography (10 g) eluting with DCM and then DCM/2M ammonia in methanol (1:1). Purify again by chromatography on silica gel (40 g) eluting with DCM/2M ammonia in methanol (1:0 to 9:1 gradient over 30 min; 35 mL/min) to obtain 7-chloro-6-(4-methyl-thiazol-2-ylthiomethyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine (0.297 g, 99%).

Workup

  1. concentrationConcentrate the reaction mixture in vacuo
  2. custompurify by SCX chromatography (10 g)
  3. washeluting with DCM
  4. customPurify again by chromatography on silica gel (40 g)
  5. washeluting with DCM/2M ammonia in methanol (1:0 to 9:1 gradient over 30 min; 35 mL/min)

Sources & evidence

ORD record
ord-2caa0dc42a7047fe8bbd152ac0c2aa4b
Source dataset
uspto-grants-2011_08
Patent number
US07994163B2

Reaction notes

Loading…