N,N-Bis(trimethylsilyl)trifluoroacetamide → [(2-Bromo-4-{[(3,4-dichloro-phenyl)-(4-phenyl-thiazol-2-yl)-amino]-methyl}-phenyl)-difluoro-methyl]-phosphonic acid

HRID 130352Notes

Reaction equation

HRID 130352 reaction equation
C([O:3][P:4]([C:9]([C:12]1[CH:17]=[CH:16][C:15]([CH2:18][N:19]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=2)[C:20]2[S:21][CH:22]=[C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:24]=2)=[CH:14][C:13]=1[Br:39])([F:11])[F:10])(=[O:8])[O:5]CC)C.C[Si](N([Si](C)(C)C)C(=O)C(F)(F)F)(C)C.I[Si](C)(C)C>C(Cl)Cl>[Br:39][C:13]1[CH:14]=[C:15]([CH2:18][N:19]([C:31]2[CH:36]=[CH:35][C:34]([Cl:37])=[C:33]([Cl:38])[CH:32]=2)[C:20]2[S:21][CH:22]=[C:23]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:24]=2)[CH:16]=[CH:17][C:12]=1[C:9]([P:4](=[O:3])([OH:5])[OH:8])([F:10])[F:11]

Participants

5

Reactant 3

HCID 65279N,N-Bis(trimethylsilyl)trifluoroacetamideHCID 85247Trimethylsilyl iodideHCID 86607370[(2-Bromo-4-{[(3,4-dichloro-phenyl)-(4-phenyl-thiazol-2-yl)-amino]-methyl}-phenyl)-difluoro-methyl]-phosphonic acid diethyl ester

Product 1

HCID 11556324[(2-Bromo-4-{[(3,4-dichloro-phenyl)-(4-phenyl-thiazol-2-yl)-amino]-methyl}-phenyl)-difluoro-methyl]-phosphonic acidYield 199.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To [(2-bromo-4-{[(3,4-dichloro-phenyl)-(4-phenyl-thiazol-2-yl)-amino]-methyl}-phenyl)-difluoro-methyl]-phosphonic acid diethyl ester (0.176 g, 0.25 mmol) in CH2Cl2 (3 mL) was added bistrimethylsilyltrifluoroacetamide (0.66 g, 2.59 mmol) and reaction mixture was stirred at room temperature for 1 h after which the reaction mixture is cooled to 20° C. and iodotrimethylsilane (0.51 g, 2.59 mmol) is added drop wise. The resulting mixture was stirred at room temperature for 1.5 hours, after which it was concentrated in vacuo. The resulting material was stirred in CH3CN (4 mL), H2O (0.5 mL), and TFA (0.5 mL) for 0.5 hours, after which it was concentrated in vacuo and partitioned between ethyl acetate and acidic Na2S2O4. The organic layer was dried over MgSO4 and concentrated in vacuo to yield 0.31 g (99%) of a white foam; 1H NMR (300 MHz, DMSO-d6) δ 7.99-7.28 (m, 12 H), 5.33 (s, 2 H); LCMS m/z 619 [M−]

Workup

  1. temperatureis cooled to 20° C.
  2. stirringThe resulting mixture was stirred at room temperature for 1.5 hours
  3. concentrationafter which it was concentrated in vacuo
  4. stirringThe resulting material was stirred in CH3CN (4 mL)
  5. waitH2O (0.5 mL), and TFA (0.5 mL) for 0.5 hours
  6. concentrationafter which it was concentrated in vacuo
  7. custompartitioned between ethyl acetate and acidic Na2S2O4
  8. dry with materialThe organic layer was dried over MgSO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-538367c3cbcb4e15b5ce81c02c08a4bb
Source dataset
uspto-grants-2008_06
Patent number
US07381736B2

Reaction notes

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