Sodium Thiosulfate → 3-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propionaldehyde

HRID 988580Notes

Reaction equation

HRID 988580 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[CH3:23][S:24]([N:27]1[CH2:32][CH2:31][C:30]2[N:33]([CH2:46][CH2:47][CH2:48][OH:49])[N:34]=[C:35]([C:36]3[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=3)[C:29]=2[CH2:28]1)(=[O:26])=[O:25].[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl.CCOCC.C([O-])(O)=O.[Na+]>[CH3:23][S:24]([N:27]1[CH2:32][CH2:31][C:30]2[N:33]([CH2:46][CH2:47][CH:48]=[O:49])[N:34]=[C:35]([C:36]3[CH:37]=[CH:38][C:39]([C:42]([F:43])([F:44])[F:45])=[CH:40][CH:41]=3)[C:29]=2[CH2:28]1)(=[O:26])=[O:25]

Participants

7

Reactant 3

HCID 24477Sodium ThiosulfateHCID 159087TriacetoxyperiodinaneHCID 222936223-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propan-1-ol

Product 1

HCID 222938973-[5-Methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propionaldehydeYield 85.2%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Dess-Martin periodinane (3.45 g, 8.2 mmol) was added to a solution of 3-[5-methanesulfonyl-3-(4-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-yl]-propan-1-ol (3.0 g, 7.4 mmol) in CH2Cl2 (20 mL) at 0° C. under N2. After 15 min, the reaction was allowed to warm to room temperature and stirred for another 1.5 h. The reaction was diluted with Et2O (60 mL) and 20% aq. NaHCO3 (35 mL) was added slowly (caution! rapid gas evolution). Then Na2S2O3 was added and stirred at room temperature for 30 min. The layers were separated and the aqueous portion was extracted with Et2O (2×30 mL). The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated. MPLC (silica, 1-10% MeOH/CH2Cl2) afforded 2.53 g of the desired aldehyde in 85% yield. MS (electrospray): exact mass calculated for C17H18F3N3O3S, 401.11; m/z found, 402.1 [M+H]. 1H NMR (400 MHz, CDCl3): 9.82 (s, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.58 (d, J=8.4 Hz, 2H), 4.68 (s, 2H), 4.25 (t, J=6.1 Hz, 2H), 3.63 (t, J=5.8 Hz, 4H), 3.14 (t, J=6.1 Hz, 2H), 2.92 (t, J=5.8 Hz, 2H), 2.81 (s, 3H).

Workup

  1. additionwas added slowly (caution! rapid gas evolution)
  2. stirringstirred at room temperature for 30 min
  3. customThe layers were separated
  4. extractionthe aqueous portion was extracted with Et2O (2×30 mL)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-94b30cc1472d47c09f72c03e3c5fca02
Source dataset
uspto-grants-2003_10
Patent number
US06635633B2

Reaction notes

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