Trifluoroacetic acid → HCID 56646838, compound

HRID 71239Notes

Reaction equation

HRID 71239 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9]2(/[CH:15]=[CH:16]/[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:39]=[CH:38][C:25]([CH2:26][N:27]5[CH2:30][CH:29]([C:31]([O:33]C(C)(C)C)=[O:32])[CH2:28]5)=[CH:24][CH:23]=4)[N:18]=3)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][C:7]=1[F:8].C(O)(C(F)(F)F)=O>>[F:1][C:2]1[CH:3]=[C:4]([C:9]2(/[CH:15]=[CH:16]/[C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:23]=[CH:24][C:25]([CH2:26][N:27]5[CH2:30][CH:29]([C:31]([OH:33])=[O:32])[CH2:28]5)=[CH:38][CH:39]=4)[N:18]=3)[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 66692303HCID 66692303, compound

Product 1

HCID 56646838HCID 56646838, compound

Procedure

(E)-tert-butyl 1-(4-(5-(2-(1-(3,4-difluorophenyl)cyclohexyl)vinyl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate (59 mg, 0.110 mmol) was dissolved in TFA (2 mL, 26.0 mmol), and the mixture was stirred for 30 mins at room temp. The acid was evaporated off, and the residue was dissolved in 2 mL of DMF and was purified by preparative LC/MS with the following conditions: Column: Waters SunFire C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 15-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing product were combined and dried via centrifugal evaporation. (E)-1-(4-(5-(2-(1-(3,4-difluorophenyl)cyclohexyl)vinyl)-1,2,4-oxadiazol-3-yl)benzyl) azetidine-3-carboxylic acid was obtained as a waxy solid (28.7 mg, 54.3% yield). LC/MS: m/e 479.7 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.95 (2H, d, J=8.28 Hz), 7.55 (1H, ddd, J=12.99, 7.97, 2.38 Hz), 7.39-7.48 (3H, m), 7.31 (1H, ddd, J=6.46, 4.33, 2.01 Hz), 7.15 (1H, d, J=16.31 Hz), 6.50 (1H, d, J=16.56 Hz), 3.65 (2H, s), 3.44 (2H, br. s.), 3.25 (3H, m), 2.08 (4H, m), 1.47 (6H, m).

Workup

  1. customThe acid was evaporated off
  2. dissolutionthe residue was dissolved in 2 mL of DMF
  3. customwas purified by preparative LC/MS with the following conditions
  4. waitGradient: 15-100% B over 25 minutes
  5. customa 5-minute hold
  6. additionFractions containing product
  7. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-ea69d8f962a948f0bb9ffe0e0896247a
Source dataset
uspto-grants-2014_09
Patent number
US08822510B2

Reaction notes

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