N-bromobutanimide → (S)-tert-butyl 1-(9-bromo-5H-chromeno[3,4-c]pyridin-8-yloxy)-4-methylpentan-2-ylcarbamate

HRID 2369515Notes

Reaction equation

HRID 2369515 reaction equation
[C:1]([O:5][C:6](=[O:29])[NH:7][CH:8]([CH2:25][CH:26]([CH3:28])[CH3:27])[CH2:9][O:10][C:11]1[CH:12]=[CH:13][C:14]2[C:24]3[C:19](=[CH:20][N:21]=[CH:22][CH:23]=3)[CH2:18][O:17][C:15]=2[CH:16]=1)([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Br:37])C(=O)C1>C(#N)C>[Br:37][C:12]1[C:11]([O:10][CH2:9][C@@H:8]([NH:7][C:6](=[O:29])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:25][CH:26]([CH3:27])[CH3:28])=[CH:16][C:15]2[O:17][CH2:18][C:19]3[C:24]([C:14]=2[CH:13]=1)=[CH:23][CH:22]=[N:21][CH:20]=3

Participants

4

Reactant 2

HCID 67184N-bromobutanimideHCID 86724429tert-butyl (1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate

Product 1

HCID 86724430(S)-tert-butyl 1-(9-bromo-5H-chromeno[3,4-c]pyridin-8-yloxy)-4-methylpentan-2-ylcarbamateYield 38.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A solution of tert-butyl(1-((5H-chromeno[3,4-c]pyridin-8-yl)oxy)-4-methylpentan-2-yl)carbamate (0.072 g, 0.181 mmol) in acetonitrile (5 mL) cooled to 0° C. and stirred for 2 min. NBS (0.029 g, 0.163 mmol) was added in single portion and the reaction mixture stirred at 0° C. for 2 h. The solvent was removed under reduced pressure and water 10 mL) was added. The product was extracted with ethyl acetate (3×15 mL). The combined organic extracts were washed with water (1×20 mL) dried over sodium sulfate and concentrated under reduced pressure. The residue was purified via preparative TLC (40% EtOAc:pet ether) to obtain (S)-tert-butyl 1-(9-bromo-5H-chromeno[3,4-c]pyridin-8-yloxy)-4-methylpentan-2-ylcarbamate (30 mg, 0.063 mmol, 35% yield). 1H NMR (400 MHz, CD3OD) δ 8.48 (d, J=5.4 Hz, 1H), 8.38 (s, 1H), 8.07 (s, 1H), 7.68 (d, J=5.4 Hz, 1H), 6.73 (s, 1H), 5.21 (s, 2 H), 4.02-3.98 (m, 3H), 1.92-1.71 (m, 1H), 1.56-1.52 (m, 2H), 0.97 (t, J=6.8 Hz, 6H).

Workup

  1. stirringthe reaction mixture stirred at 0° C. for 2 h
  2. customThe solvent was removed under reduced pressure and water 10 mL)
  3. additionwas added
  4. extractionThe product was extracted with ethyl acetate (3×15 mL)
  5. washThe combined organic extracts were washed with water (1×20 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified via preparative TLC (40% EtOAc:pet ether)

Sources & evidence

ORD record
ord-8514590cf02e479ebb20d1f98fa4ae1b
Source dataset
uspto-grants-2014_04
Patent number
US08703953B2

Reaction notes

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