Water → HCID 86600694, compound

HRID 1191524Notes

Reaction equation

HRID 1191524 reaction equation
I[CH2:2][C@@H:3]([CH3:16])[CH2:4][N:5]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[O:8][CH2:7][C:6]1=[O:15].[Cl-].[CH2:18]([O:20][N:21]=[C:22]1[CH2:28][CH:27]2[NH2+:29][CH:24]([CH2:25][CH2:26]2)[CH2:23]1)[CH3:19].C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH2:18]([O:20][N:21]=[C:22]1[CH2:28][CH:27]2[N:29]([CH2:2][C@@H:3]([CH3:16])[CH2:4][N:5]3[C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[O:8][CH2:7][C:6]3=[O:15])[CH:24]([CH2:25][CH2:26]2)[CH2:23]1)[CH3:19]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 68912224(S)-4-(3-Iodo-2-methylpropyl]-4H-benzo[1,4]oxazin-3-oneHCID 86600695HCID 86600695, compound

Product 1

HCID 86600694HCID 86600694, compoundYield 24.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A 7 ml vial was charged with 4-(3-iodo-2(S)-methyl-propyl)-4H-benzo[1,4]oxazin-3-one (330 mg, 1.0 mmol), crude 3-ethoxyimino-8-azonia-bicyclo[3.2.1]octane chloride (200 mg, 0.98 mmol), and K2CO3 (290 mg, 2.1 mmol) in dry DMF (4 ml) and the reaction was shaken at 60° C. for 3 days. The reaction was then poured into water and extracted with ether. The combined organic phases were washed brine, dried (Na2SO4), filtered, concentrated under reduced pressure and the oily residue was purified by flash column chromatography (SiO2; CH2Cl2/acetone/MeOH, 90:7:3) to yield the diastereomeric mixture of the title compound as an oil (87 mg, 0.24 mmol, 24%). 1H NMR (CD3OD) δ 7.28 (dd, J=2.0, 7.6 Hz, 1H), 7.07-6.93 (m, 3H), 4.57 (ABq, J=14.8, 19.6 Hz, 2H), 4.12 (dd, J=6.4, 14.4 Hz, 1H), 4.05-3.92 (m, 3H), 3.30-3.16 (m, 2H), 2.92-2.82 (m, 1H), 2.54-2.32 (m, 3H), 2.18-1.81 (m, 2H), 1.60-1.34 (m, 2H), 1.20 (m, 3H), 0.93 (d, J=6.8H); 13C NMR (CD3OD) δ165.8, 156.6, 146.0, 128.6, 124.0, 122.6, 116.8, 115.9, 68.5, 67.4, 60.2, 59.54, 59.48, 58.8, 56.5, 45.0, 37.0, 36.9, 31.9, 31.7, 30.99, 30.96, 27.6, 27.0, 26.7, 26.1, 15.9, 13.7; HPLC-MS (ammonium acetate) [M+H]+=372.21.

Workup

  1. extractionextracted with ether
  2. washThe combined organic phases were washed brine
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customthe oily residue was purified by flash column chromatography (SiO2; CH2Cl2/acetone/MeOH, 90:7:3)
  7. customto yield

Sources & evidence

ORD record
ord-002c7dc9b76747f8809b7a58684779f3
Source dataset
uspto-grants-2014_03
Patent number
US08680115B2

Reaction notes

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