Formic Acid → HCID 11364363, compound

HRID 1723809Notes

Reaction equation

HRID 1723809 reaction equation
[CH:1](O)=[O:2].C(OC(=O)C)(=O)C.[OH:11][NH:12][CH:13]([CH2:22][S:23]([N:26]1[CH2:31][CH2:30][N:29]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH2:39][C:40]([F:43])([F:42])[F:41])=[CH:34][N:33]=2)[CH2:28][CH2:27]1)(=[O:25])=[O:24])[CH2:14][CH2:15][C:16]1[N:21]=[CH:20][CH:19]=[CH:18][N:17]=1>C(Cl)Cl>[OH:11][N:12]([C@H:13]([CH2:22][S:23]([N:26]1[CH2:27][CH2:28][N:29]([C:32]2[CH:37]=[CH:36][C:35]([O:38][CH2:39][C:40]([F:43])([F:42])[F:41])=[CH:34][N:33]=2)[CH2:30][CH2:31]1)(=[O:25])=[O:24])[CH2:14][CH2:15][C:16]1[N:17]=[CH:18][CH:19]=[CH:20][N:21]=1)[CH:1]=[O:2]

Participants

5

Reactant 3

HCID 284Formic Acid2×HCID 7918Acetic AnhydrideHCID 11705851HCID 11705851, compound

Product 1

HCID 11364363HCID 11364363, compoundYield 906.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To formic acid (54 mL, 1.4 mol) at 8° C. was added acetic anhydride (11 mL, 100 mmol) and the mixture was stirred at RT for 10 minutes. The mixed anhydride was then recooled to 8° C., and added to a solution, pre-cooled to 0° C., 2-[3-(hydroxyamino)-4-({4-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]piperazin-1-yl}sulfonyl)butyl]pyrimidine (16.32 g, 33.3 mmol) in DCM (170 mL) and formic acid (65 mL, 1.7 mol). The reaction was brought to room temperature and stirred for one hour. Volatiles were then removed in vacuo, and the residue azeotroped with toluene (2×50 mL). The residue was then dissolved in MeOH/DCM (1:1, 250 mL) and stirred overnight at room temperature. The solution was then concentrated in vacuo, and partitioned between DCM (250 mL) and sat. NaHCO3 (250 mL). The DCM layer was then filtered through silica gel (20 g) washing with 5% MeOH/DCM and the volatiles removed in vacuo to give the racemic title compound as a pale yellow foam (15.68 g, 302 mmol, 91%).

Workup

  1. customwas then recooled to 8° C.
  2. additionadded to a solution
  3. temperaturepre-cooled to 0° C.
  4. customwas brought to room temperature
  5. stirringstirred for one hour
  6. customVolatiles were then removed in vacuo
  7. customthe residue azeotroped with toluene (2×50 mL)
  8. dissolutionThe residue was then dissolved in MeOH/DCM (1:1, 250 mL)
  9. stirringstirred overnight at room temperature
  10. concentrationThe solution was then concentrated in vacuo
  11. custompartitioned between DCM (250 mL) and sat. NaHCO3 (250 mL)
  12. filtrationThe DCM layer was then filtered through silica gel (20 g)
  13. washwashing with 5% MeOH/DCM
  14. customthe volatiles removed in vacuo

Sources & evidence

ORD record
ord-ed3342cf644e426a94f7cec152e5e1bf
Source dataset
uspto-grants-2009_02
Patent number
US07485644B2

Reaction notes

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