Diazomethane → HCID 90409108, compound

HRID 1855090Notes

Reaction equation

HRID 1855090 reaction equation
[OH-].[K+].CN(N=O)C(N[N+]([O-])=O)=N.[N+](=[CH2:15])=[N-].[F:16][C:17]1[CH:18]=[C:19]([C:30]23[CH2:37][CH2:36][C:33]([CH2:38][CH2:39]/[CH:40]=[CH:41]/[C:42]([O:44][CH3:45])=[O:43])([CH2:34][CH2:35]2)[CH2:32][O:31]3)[CH:20]=[C:21]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[CH:22]=1>C1COCC1.O.CCOCC>[F:16][C:17]1[CH:18]=[C:19]([C:30]23[CH2:35][CH2:34][C:33]([CH2:38][CH2:39][CH:40]4[CH2:15][CH:41]4[C:42]([O:44][CH3:45])=[O:43])([CH2:36][CH2:37]2)[CH2:32][O:31]3)[CH:20]=[C:21]([O:23][CH:24]2[CH2:29][CH2:28][CH2:27][CH2:26][O:25]2)[CH:22]=1

Participants

8

Reactant 4

HCID 9550Diazomethane2×HCID 14797Potassium HydroxideHCID 90408793HCID 90408793, compoundHCID 135436526N-Methyl-N'-nitro-N-nitrosoguanidine

Product 1

HCID 90409108HCID 90409108, compoundYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a vigorously stirred 0° C. biphasic solution of Et2O (10 mL), 40% aq. KOH (2 mL, 14.0 mmol) and water (2 mL) was added portionwise N-methyl-N′-nitro-N-nitrosoguanidine (0.844 g, 2.87 mmol) over 15 min. When addition had been completed, the ether layer was separated and dried with KOH pellets. The contents were allowed to stand for 5 min, then redried over fresh KOH pellets. To 5 mL of the diazomethane solution (˜50% of total volume) was added a 0° C. solution of (E)-methyl 5-(1-(3-fluoro-5-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)pent-2-enoate (0.3 g, 0.717 mmol) in THF (2 mL). A mixture of PdOAc2 (0.016 g, 0.072 mmol) in THF (2 mL) was added slowly and the reaction was stirred at 0° C. for 15 min and then the remainder of the diazomethane solution (˜5 mL) was added slowly. The reaction was allowed to warm to rt and stirred for 1 h, then was filtered and then concentrated in vacuo. The residual crude oil was chromatographed (SiO2; gradient from 0% to 30% EtOAc/hexane over 10 min) to give the title compound (0.26 g, 0.601 mmol, 84% yield) as a clear oil. 1H NMR (CDCl3) δ: 6.86 (t, J=1.8 Hz, 1H), 6.74 (ddd, J=10.1, 2.4, 1.5 Hz, 1H), 6.68 (dt, J=10.5, 2.3 Hz, 1H), 5.40 (t, J=3.2 Hz, 1H), 3.93-3.84 (m, 1H), 3.83-3.76 (m, 2H), 3.68 (s, 3H), 3.62 (dtt, J=11.4, 4.1, 1.9 Hz, 1H), 2.03-1.94 (m, 5H), 1.88-1.81 (m, 2H), 1.75-1.56 (m, 7H), 1.43-1.16 (m, 7H), 0.75-0.68 (m, 1H); 19F NMR (CDCl3) δ: −112.1.

Workup

  1. additionWhen addition
  2. customthe ether layer was separated
  3. dry with materialdried with KOH pellets
  4. dry with materialredried over fresh KOH pellets
  5. additionwas added slowly
  6. temperatureto warm to rt
  7. stirringstirred for 1 h
  8. filtrationwas filtered
  9. concentrationconcentrated in vacuo
  10. customThe residual crude oil was chromatographed (SiO2; gradient from 0% to 30% EtOAc/hexane over 10 min)

Sources & evidence

ORD record
ord-6f26f98bd82d4ab789f38a9676e4f42e
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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