Trifluoroacetic acid → HCID 73506446, compound

HRID 1508320Notes

Reaction equation

HRID 1508320 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[C:11]([C:17]2([C:34]([F:37])([F:36])[F:35])[O:21][N:20]=[C:19]([C:22]3[CH:23]=[C:24]4[C:28](=[CH:29][CH:30]=3)[C:27]3([CH2:33][NH:32][CH2:31]3)[O:26][CH2:25]4)[O:18]2)[CH:12]=[C:13]([Cl:16])[C:14]=1[F:15].C(N(CC)CC)C.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH3:67][S:68]([CH2:71][C:72](O)=[O:73])(=[O:70])=[O:69]>CN(C=O)C>[Cl:8][C:9]1[CH:10]=[C:11]([C:17]2([C:34]([F:36])([F:37])[F:35])[O:21][N:20]=[C:19]([C:22]3[CH:23]=[C:24]4[C:28](=[CH:29][CH:30]=3)[C:27]3([CH2:33][N:32]([C:72](=[O:73])[CH2:71][S:68]([CH3:67])(=[O:70])=[O:69])[CH2:31]3)[O:26][CH2:25]4)[O:18]2)[CH:12]=[C:13]([Cl:16])[C:14]=1[F:15]

Participants

8

Reactant 6

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 37328412-Methanesulfonylacetic acidHCID 118252746HCID 118252746, compound

Product 1

HCID 73506446HCID 73506446, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of trifluoroacetic acid salt of 5′-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-1,4,2-dioxazol-3-yl)-3′H-spiro[azetidine-3,1′-isobenzofuran](Preparation 45, 0.3 g, 0.648 mmol, 1 eq) in DMF (5 mL) was added triethyl amine (0.727 mL, 5.181mmol, 8 eq), followed by addition of EDC.HCl (0.185 g, 0.971 mmol, 1.5 eq), HOBt (0.087 g, 0.648 mmol, 1 eq) and methane sulfonyl acetic acid (0.178 g, 1.295 mmol, 2 eq) at room temperature. Resulting reaction mixture was stirred at room temperature for 18 hours under nitrogen atmosphere. After complete consumption of starting material, reaction mixture was quenched by water (50 mL) and extracted with ethyl acetate (3×30 mL). Combined organic phase was washed with saturated solution of LiCl solution (30 mL), brine (30 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure to get brown thick oil (0.48 g, crude). Crude was purified by combiflash using 40 g Redisep column. Desired compound was eluted in 52% ethyl acetate in hexane to afford title compound as off white solid (0.228 g, 60.35%). 1H NMR (400 MHz, CDCl3) δ: 3.19 (s, 3H), 3.86 (s, 2H), 4.35 (d, J=11.16 Hz, 1H), 4.45 (d, J=11.16 Hz, 1H), 4.67 (t, J=10.72 Hz, 2H), 5.19 (s, 2H), 7.63-7.66 (m, 3H), 7.70 (s, 1H), 7.89 (d, J=8.08 Hz, 1H). (m/z): 580.9 (M−H), HPLC Purity: 95.78%.

Workup

  1. customResulting
  2. customreaction mixture
  3. customAfter complete consumption of starting material, reaction mixture
  4. customwas quenched by water (50 mL)
  5. extractionextracted with ethyl acetate (3×30 mL)
  6. washCombined organic phase was washed with saturated solution of LiCl solution (30 mL), brine (30 mL)
  7. dry with materialdried over anhydrous Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customto get brown thick oil (0.48 g, crude)
  10. customCrude was purified by combiflash
  11. washDesired compound was eluted in 52% ethyl acetate in hexane

Sources & evidence

ORD record
ord-00c58d229a4a48d9bb988710b332d569
Source dataset
uspto-grants-2015_12
Patent number
US09221835B2

Reaction notes

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