2,6-Lutidine → HCID 72472529, compound

HRID 564353Notes

Reaction equation

HRID 564353 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]23[CH2:26][CH2:25][CH:24]([O:27][CH2:28][CH2:29][NH2:30])[CH2:23][CH:12]2[CH2:13][O:14][C:15]2[C:20]3=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[F:22])(=[O:10])=[O:9])=[CH:4][CH:3]=1.N1C(C)=CC=CC=1C.[O:39](S(C(F)(F)F)(=O)=O)[S:40]([C:43]([F:46])([F:45])[F:44])(=O)=[O:41]>C(Cl)Cl.[NH4+].[Cl-]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([C:11]23[CH2:26][CH2:25][CH:24]([O:27][CH2:28][CH2:29][NH:30][S:40]([C:43]([F:46])([F:45])[F:44])(=[O:41])=[O:39])[CH2:23][CH:12]2[CH2:13][O:14][C:15]2[C:20]3=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[F:22])(=[O:9])=[O:10])=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 79372,6-LutidineHCID 67749Trifluoromethanesulfonic anhydrideHCID 67006731HCID 67006731, compound

Product 1

HCID 72472529HCID 72472529, compoundYield 30%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent

Procedure

A solution of 2-[10a-(4-chloro-benzene sulfonyl)-1,4-difluoro-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-8-yloxy]-ethylamine (71 mg, 0.168 mmol) in CH2Cl2 (5 mL) at −78° C. was treated with 2,6-lutidine (33 μL, 0.284 mmol), Tf2O (45 μL, 0.948 mmol) and warmed slowly to ambient temperature. After 17 h, the reaction mixture was diluted with saturated aqueous NH4Cl and extracted with CH2Cl2 (2×). The combined organic extracts were washed with saturated aqueous NaHCO3, dried over MgSO4, and concentrated in vacuo. The residue was purified by preparative-chromatography over silica gel (eluted in hexanes/EtOAc 1:1) to afford the title compound (29 mg, 30%): 1H NMR (CDCl3 400 MHz) δ 7.61 (d, J=8.8 Hz, 2H), 7.48 (d, J=8.8 Hz, 2H), 7.08 (m, 1H), 6.44 (m, 1H), 5.22 (dd, J=11.7, 2.9 Hz, 1H), 4.12 (d, J=11.7 Hz, 1H), 3.57 (m, 3H), 3.01 (m, 1H), 2.56 (m, 1H), 2.33 (m, 1H), 1.91 (m, 2H), 1.56 (m, 1H), 1.15 (m, 2H).

Workup

  1. extractionextracted with CH2Cl2 (2×)
  2. washThe combined organic extracts were washed with saturated aqueous NaHCO3
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative-chromatography over silica gel (eluted in hexanes/EtOAc 1:1)

Sources & evidence

ORD record
ord-9d0127bef8c14f2a827263882638dc49
Source dataset
uspto-grants-2011_11
Patent number
US08067621B2

Reaction notes

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