Triacetoxyperiodinane → 1-(3-Oxo-propyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 970127Notes

Reaction equation

HRID 970127 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][C:33]2[N:36]([CH2:49][CH2:50][CH2:51][OH:52])[N:37]=[C:38]([C:39]3[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:47])[F:46])=[CH:41][CH:40]=3)[C:32]=2[CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]>C(Cl)Cl.CCOCC.C([O-])(O)=O.[Na+]>[C:23]([O:27][C:28]([N:30]1[CH2:35][CH2:34][C:33]2[N:36]([CH2:49][CH2:50][CH:51]=[O:52])[N:37]=[C:38]([C:39]3[CH:44]=[CH:43][C:42]([C:45]([F:48])([F:46])[F:47])=[CH:41][CH:40]=3)[C:32]=2[CH2:31]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 2

HCID 159087TriacetoxyperiodinaneHCID 684611921-(3-Hydroxy-propyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

Product 1

HCID 865848181-(3-Oxo-propyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl esterYield 79%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

Dess-Martin periodinane (1.43 g, 3.36 mmol) was added portion wise to a stirred solution of 1-(3-hydroxy-propyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (1.30 g, 3.05 mmol) in CH2Cl2 (15 mL) at 0° C. under N2. Then the reaction was stirred at 0° C. for 15 min and allowed to warm to room temperature. After stirring at room temperature for 1.5 h the reaction was diluted with Et2O (50 mL) and saturated NaHCO3 (15 mL) was added slowly (caution! gas evolution). Then Na2S2O3.5H2O (5.31 g, 21.4 mmol) was added and stirred for 30 min. The layers were separated and the aqueous layer was extracted with Et2O (2×30 mL). The combined extracts were washed with brine, dried (Na2SO4) and concentrated. MPLC (1-10% MeOH/CH2Cl2) afforded the aldehyde in 79% yield (1.02 g). TLC (silica, 10% MeOH/CH2Cl2): Rf=0.67. MS (electrospray) calculated for C21H24F3N3O3, 424.2 ([M+H]+), m/z found, 424.2. 1H NMR (400 MHz, CDCl3): 9.82 (s, 1H), 7.65 (br d, J=8.0 Hz, 2H), 7.54 (br s, 2H), 4.53 (s, 2H), 4.21 (t, J=6.2 Hz, 2H), 3.68 (br s, 2H), 3.04 (t, J=6.2 Hz, 2H), 2.70 (t, J=5.6 Hz, 2H), 1.39 (s, 9H).

Workup

  1. temperatureto warm to room temperature
  2. stirringAfter stirring at room temperature for 1.5 h the reaction
  3. additionwas added slowly (caution! gas evolution)
  4. stirringstirred for 30 min
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with Et2O (2×30 mL)
  7. washThe combined extracts were washed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-4f2de8fff1a34a87a40886c4621040d8
Source dataset
uspto-grants-2007_12
Patent number
US07309703B2

Reaction notes

Loading…