Sodium Azide → (S)-2'-azido-7'-methoxy-5H-spiro[oxazole-4,9'-xanthen]-2-amine

HRID 1970308Notes

Reaction equation

HRID 1970308 reaction equation
Br[C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:16][CH3:17])=[CH:9][CH:10]=3)[C@:5]3([CH2:21][O:20][C:19]([NH2:22])=[N:18]3)[C:4]=2[CH:3]=1.[N-:23]=[N+:24]=[N-:25].[Na+].[Na].O=C1O[C@H]([C@H](CO)O)C(O)=C1O.CN[C@@H]1CCCC[C@H]1NC>CCO.O.[Cu]I>[N:23]([C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:16][CH3:17])=[CH:9][CH:10]=3)[C@:5]3([CH2:21][O:20][C:19]([NH2:22])=[N:18]3)[C:4]=2[CH:3]=1)=[N+:24]=[N-:25]

Participants

8

Reactant 4

HCID 33557Sodium AzideHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 59272314(R)-2'-bromo-7'-methoxy-5H-spiro[oxazole-4,9'-xanthen]-2-amineHCID 66586226sodium L-ascorbic acid

Product 1

HCID 86640718(S)-2'-azido-7'-methoxy-5H-spiro[oxazole-4,9'-xanthen]-2-amine

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A 5 mL smith synthesizer vial was charged with (R)-2′-bromo-7′-methoxy-5H-spiro[oxazole-4,9′-xanthen]-2-amine (1.248 g, 3.46 mmol), sodium azide (0.684 g, 10.52 mmol), L-ascorbic acid sodium salt (0.057 g, 0.288 mmol), copper(I) iodide (0.131 g, 0.688 mmol), and (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (0.116 mL, 0.736 mmol) in EtOH (6.0 mL), water (2.6 mL) and the reaction was heated to 100° C. in the microwave for 35 minutes. The reaction vial was cooled to RT and concentrated on the rotary evaporator and the resulting residue was taken up in ethyl acetate (125 mL), water (50 mL) the organic layer was separated. The organic layer was dried over sodium sulfate and concentrated to yield the crude product which was purified by silica gel flash column chromatography (using a 40G ISCO silica gel cartridge), and eluted using hexanes/ethyl acetate gradient. The fractions were combined and concentrated to yield (S)-2′-azido-7′-methoxy-5H-spiro[oxazole-4,9′-xanthen]-2-amine as a yellowish solid. MS (ESI pos. ion) m/z: 324 (M+1).

Workup

  1. customThe reaction
  2. temperaturevial was cooled to RT
  3. concentrationconcentrated on the rotary evaporator
  4. customwater (50 mL) the organic layer was separated
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. concentrationconcentrated
  7. customto yield the crude product which
  8. customwas purified by silica gel flash column chromatography (
  9. washeluted
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-103aa626ae2b4d49b14d6fc254007bf4
Source dataset
uspto-grants-2013_04
Patent number
US08426447B2

Reaction notes

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