Trifluoroacetic acid → HCID 71554976, compound

HRID 2407535Notes

Reaction equation

HRID 2407535 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]2[C:14]3([CH2:17][N:16]([C:18](OC(C)(C)C)=[O:19])[CH2:15]3)[CH2:13][CH2:12]2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.FC(F)(F)C(O)=O.[Cl:32][C:33]1[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=1[CH2:40][N:41]=C=O.C(N(CC)CC)C>ClCCl.C(#N)C>[Cl:32][C:33]1[CH:38]=[C:37]([Cl:39])[CH:36]=[CH:35][C:34]=1[CH2:40][NH:41][C:18]([N:16]1[CH2:15][C:14]2([N:11]([S:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)(=[O:9])=[O:10])[CH2:12][CH2:13]2)[CH2:17]1)=[O:19]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acid2×HCID 8471TriethylamineHCID 46127082,4-Dichlorobenzyl isocyanateHCID 86682348HCID 86682348, compound

Product 1

HCID 71554976HCID 71554976, compoundYield 91.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 1-(4-fluorophenylsulfonyl)-1,6-diazaspiro[3.3]heptane-6-carboxylate (452 mg, 1.27 mmol) in dichloromethane (8 mL) was added trifluoroacetic acid (489 μl, 6.34 mmol). After 2 h at ambient temperature, another amount of trifluoroacetic acid was added (300 μl, 3.89 mmol). The reaction mixture was stirred for 1.5 h at ambient temperature and concentrated under reduced pressure. The residue was partitioned in toluene (10 mL) and then concentrated, this procedure was repeated twice to give the unpurified amine (540 mg), which was used directly in the next step without further purification. To a solution of the obtained 1-(4-fluorophenylsulfonyl)-1,6-diazaspiro[3.3]heptanes in acetonitrile (10 mL) was added 2,4-dichloro-1-(isocyanatomethyl)benzene (216 μl, 1.47 mmol) followed by triethylamine (294 μl, 2.11 mmol) and the mixture was stirred for 1 h at ambient temperature. The solvent was evaporated in vacuo and the resulting solid was purified by chromatography (SiO2; heptane:ethyl acetate 1:4 to dichloromethane/methanol/ammonia 95:4.5:0.5) to give the titled compound (530 mg, 91%) as colorless solid. HRMS (EI): 457.0431 (exact mass calculated for C19H17Cl2FN3O3S ([M]+)=457.0430).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was partitioned in toluene (10 mL)
  3. concentrationconcentrated
  4. customto give the unpurified amine (540 mg), which
  5. customwas used directly in the next step without further purification
  6. stirringthe mixture was stirred for 1 h at ambient temperature
  7. customThe solvent was evaporated in vacuo
  8. customthe resulting solid was purified by chromatography (SiO2; heptane:ethyl acetate 1:4 to dichloromethane/methanol/ammonia 95:4.5:0.5)

Sources & evidence

ORD record
ord-dfb894586aee496a89eecd6b6de25e43
Source dataset
uspto-grants-2014_08
Patent number
US08809552B2

Reaction notes

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