1,2-Dichloroethane → HCID 90409507, compound

HRID 1855093Notes

Reaction equation

HRID 1855093 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:17]23[CH2:24][CH2:23][C:20]([CH2:25][CH2:26][O:27][CH2:28][C:29](O)=[O:30])([CH2:21][CH2:22]2)[CH2:19][O:18]3)[CH:5]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([F:16])[CH:10]=2)[CH:7]=1.C1C=CC2[N:40]([OH:41])N=NC=2C=1.[CH2:42](Cl)[CH2:43]Cl.CN(C=O)C.[CH2:51]1C[O:54][CH2:53][CH2:52]1>>[F:1][C:2]1[CH:3]=[C:4]([C:17]23[CH2:24][CH2:23][C:20]([CH2:25][CH2:26][O:27][CH2:28][C:29]([NH:40][O:41][CH:43]4[CH2:42][CH2:51][CH2:52][CH2:53][O:54]4)=[O:30])([CH2:21][CH2:22]2)[CH2:19][O:18]3)[CH:5]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([CH3:15])=[C:11]([F:16])[CH:10]=2)[CH:7]=1

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 757711-HydroxybenzotriazoleHCID 78319123HCID 78319123, compound

Product 1

HCID 90409507HCID 90409507, compoundYield 96%

Procedure

To a mixture of 2-(2-(1-(3-fluoro-5-(3-fluoro-4-methylphenoxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)ethoxy)acetic acid (23 mg, 0.053 mmol), HOBT (10 mg, 0.064 mmol), EDC (12 mg, 0.064 mmol) in THF (1 mL)/DMF (1 mL) was added 0-(tetrahydro-2H-pyran-2-yl)hydroxylamine (7.5 mg, 0.064 mmol) and TEA (0.074 mL, 0.53 mmol). The reaction mixture was stirred at rt overnight. After volatiles were removed in vacuo, the residue was dissolved in EtOAc (5 mL), then successively washed with 10% aq. citric acid (5 mL), sat′d aq. NaHCO3 (5 mL) and water (5 mL). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo. The crude product (oil) was chromatographed [SiO2; gradient of EtOAc/hexanes (0% to 50% over 10 min)] to give the title compound (27 mg, 0.051 mmol, 96% yield) as a clear oil. [M+Na]+=554.4; 1H NMR (CDCl3) δ: 8.92 (s, 1H), 7.13 (t, J=8.7 Hz, 1H), 6.91-6.81 (m, 2H), 6.74-6.65 (m, 2H), 6.53 (dt, J=9.7, 2.3 Hz, 1H), 4.99 (t, J=3.0 Hz, 1H), 4.06-3.91 (m, 3H), 3.83 (s, 2H), 3.66 (dtd, J=11.3, 4.0, 1.7 Hz, 1H), 3.54 (t, J=6.9 Hz, 2H), 2.25 (d, J=2.0 Hz, 3H), 2.03-1.94 (m, 4H), 1.91-1.77 (m, 3H), 1.76-1.55 (m, 7H), 1.50 (t, J=6.8 Hz, 2H); 19F NMR (CDCl3) δ: −110.95, −114.13.

Workup

  1. customAfter volatiles were removed in vacuo
  2. dissolutionthe residue was dissolved in EtOAc (5 mL)
  3. washsuccessively washed with 10% aq. citric acid (5 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product (oil) was chromatographed [SiO2; gradient of EtOAc/hexanes (0% to 50% over 10 min)]

Sources & evidence

ORD record
ord-f20d1306c3f0464e923aaec5543834c4
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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