Acetic Acid → 1,1,1-trifluoro-N-((3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)pyridin-4-yl)methyl)methane-sulfonamide

HRID 1253917Notes

Reaction equation

HRID 1253917 reaction equation
[CH3:1][N:2]1[C:6]2[CH:7]=[C:8]([C:11]3[CH:18]=[N:17][CH:16]=[CH:15][C:12]=3[CH:13]=O)[CH:9]=[CH:10][C:5]=2[O:4][C:3]1=[O:19].[F:20][C:21]([F:27])([F:26])[S:22]([NH2:25])(=[O:24])=[O:23].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[F:20][C:21]([F:27])([F:26])[S:22]([NH:25][CH2:13][C:12]1[CH:15]=[CH:16][N:17]=[CH:18][C:11]=1[C:8]1[CH:9]=[CH:10][C:5]2[O:4][C:3](=[O:19])[N:2]([CH3:1])[C:6]=2[CH:7]=1)(=[O:24])=[O:23]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 79001TrifluoromethylsulfonamideHCID 5049666Sodium triacetoxyborohydrideHCID 866633583-(3-Methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)isonicotinaldehyde

Product 1

HCID 498017171,1,1-trifluoro-N-((3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)pyridin-4-yl)methyl)methane-sulfonamideYield 22.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of 3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)isonicotinaldehyde (128 mg, 0.5 mmol), trifluoromethanesulfonamide (94 mg, 0.63 mmol), acetic acid (60.5 mg, 1 mmol) and 4° A molecular sieves in 1,2-dichloroentane (2 mL) heated at 70° C. under nitrogen for 6 h. The suspension was cooled to room temperature and sodium triacetoxyborohydride (excess amount) was added. The reaction mixture was further stirred at room temperature for an additional 15 h. The mixture was diluted with dichloromethane (20 mL) and filtered through a pad of celite. The filter cake was thoroughly washed with an additional 30 mL of dichloromethane. The combined filtrates were washed with NaHCO3 (saturated solution). The aqueous phase was extracted with dichloromethane (2×50 mL). The organic phases were combined, dried over anhydrous Na2SO4. After filtration and concentration, the residue was purified by flash column (0-100% ethyl acetate in heptane, v/v) and yielded 43 mg of 1,1,1-trifluoro-N-((3-(3-methyl-2-oxo-2,3-dihydrobenzo[d]oxazol-5-yl)pyridin-4-yl)methyl)methane-sulfonamide as colorless solid ESI-MS m/z; 388.0 [M+1]+, Retention time 1.19 min; 1HNMR (MeOD, 400.342 MHz): δ 3.43 (s, 3H), 4.41 (5, 2H), 7.12 (dd, J=8.2, 1.8 Hz, 1H), 7.15 (s, 1H), 7.21 (d, J=1.6 Hz, 1H), 760 (d, J=5.2 Hz, 1H), 8.46 (s, 1H), 8.60 (d, J=8.2 Hz, 1H); and 5-(4-(hydroxymethyl)pyridin-3-yl)-3-methylbenzo[d]oxazol-2(3H)-one 37 mg as pinkish solid ESI-MS m/z: 257.0 [M+1]+, Retention time 0.84 min; 1HNMR (MeOD, 400.342 MHz): δ 3.3 (s, 3H), 4.41 (s, 2H), 7.12 (dd, J=1.76, 8.2 Hz, 1H), 7.21 (d, J=1.56 Hz, 1H), 7.37 (d, J=8.2 Hz, 1H), 7.60 (d, J=5.2 Hz, 1H), 8.46 (s, 1H), 8.60 (d. J=5.2 Hz, 1H).

Workup

  1. temperatureThe suspension was cooled to room temperature
  2. filtrationfiltered through a pad of celite
  3. washThe filter cake was thoroughly washed with an additional 30 mL of dichloromethane
  4. washThe combined filtrates were washed with NaHCO3 (saturated solution)
  5. extractionThe aqueous phase was extracted with dichloromethane (2×50 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationAfter filtration and concentration
  8. customthe residue was purified by flash column (0-100% ethyl acetate in heptane, v/v)

Sources & evidence

ORD record
ord-6fafecc8091143cc8db383609cf2b969
Source dataset
uspto-grants-2013_06
Patent number
US08455522B2

Reaction notes

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