Neopentyl alcohol → (S)-7-bromo-3-methoxy-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

HRID 455649Notes

Reaction equation

HRID 455649 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C@:15]3([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)[C:14]3[CH:13]=[C:12](Cl)[N:11]=[CH:10][C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.CC(C)(C)[CH2:25][OH:26].C1OCCOCCOCCOCCOCCOC1.[OH-].[K+]>>[Br:1][C:2]1[CH:3]=[C:4]2[C@:15]3([N:20]=[C:19]([NH2:21])[CH2:18][O:17][CH2:16]3)[C:14]3[CH:13]=[C:12]([O:26][CH3:25])[N:11]=[CH:10][C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 6404Neopentyl alcoholHCID 14797Potassium HydroxideHCID 2855718-Crown-6HCID 58465879(S)-7-bromo-3-chloro-2',6'-dihydrospiro[chromeno [2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amine

Product 1

HCID 58465867(S)-7-bromo-3-methoxy-2',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,3'-[1,4]oxazin]-5'-amineYield 52.9%

Procedure

A microwave vial was charged with (S)-7-bromo-3-chloro-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine (1.2557 g, 3.30 mmol), 2,2-dimethylpropan-1-ol (0.914 g, 10.37 mmol), 18-crown-6 (0.087 g, 0.330 mmol), and potassium hydroxide (0.925 g, 16.50 mmol) (freshly ground). The vial was flushed with Ar (g), then dioxane (6.60 mL) was added. The vial was sealed and placed in a 120° C. oil bath and stirred for 24 hours. The reaction mixture was diluted with water and a small amount of brine. The aq. mixture was then extracted with EtOAc (3×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography (0-100% EtOAc/hexanes) to afford 0.657 g of (S)-7-bromo-3-methoxy-2′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,3′-[1,4]oxazin]-5′-amine as a yellow solid.

Workup

  1. customThe vial was flushed with Ar (g)
  2. additiondioxane (6.60 mL) was added
  3. customThe vial was sealed
  4. customplaced in a 120° C.
  5. additionThe reaction mixture was diluted with water
  6. extractionThe aq. mixture was then extracted with EtOAc (3×)
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by chromatography (0-100% EtOAc/hexanes)

Sources & evidence

ORD record
ord-1f9ac4c8e54a49aeb23a78256c4518e6
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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