Ethanol → (S)-7-azido-3-chloro-1-fluoro-5',6'-dihydrospiro[chromeno[2,3-c]pyridine-5,4'-[1,3]oxazin]-2'-amine

HRID 931643Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C@@:15]3([CH2:20][CH2:19][O:18][C:17]([NH2:21])=[N:16]3)[C:14]3[CH:13]=[C:12]([Cl:22])[N:11]=[C:10]([F:23])[C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1.[N-:24]=[N+:25]=[N-:26].[Na+].CCO>[Cu]I.O>[N:24]([C:2]1[CH:3]=[C:4]2[C@@:15]3([CH2:20][CH2:19][O:18][C:17]([NH2:21])=[N:16]3)[C:14]3[CH:13]=[C:12]([Cl:22])[N:11]=[C:10]([F:23])[C:9]=3[O:8][C:5]2=[CH:6][CH:7]=1)=[N+:25]=[N-:26]

Participants

Conditions

Temperature: 85 °C

Procedure

A microwave vial was charged with (S)-7-bromo-3-chloro-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazin]-2′-amine (2.08 g, 5.22 mmol), (+)-sodium 1-ascorbate (0.103 g, 0.522 mmol), sodium azide (0.550 ml, 15.65 mmol) and copper(i) iodide (0.035 ml, 1.044 mmol). The vial was sealed, purged with N2 and followed by the addition of trans-n,n′-dimethyl-1,2-cyclohexanediamine (0.247 ml, 1.565 mmol), EtOH (12 mL) and water (4.6 mL). The resulting mixture was heated at 85° C. for 1.5 h. The mixture was poured into water and extracted with EtOAc. The combined organics were washed with brine, dried over Na2SO4, filtered, concentrated and chromatographed on silica gel using 0-50% MeOH/DCM to afford a light yellow solid as (S)-7-azido-3-chloro-1-fluoro-5′,6′-dihydrospiro[chromeno[2,3-c]pyridine-5,4′-[1,3]oxazin]-2′-amine (0.86 g, 45.7% yield).

Workup

customThe vial was sealed
custompurged with N2
extractionextracted with EtOAc
washThe combined organics were washed with brine
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customchromatographed on silica gel using 0-50% MeOH/DCM

Sources & evidence

ORD record: ord-cafd1ad408d44a9182756c2ffeb70c10
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296759B2

Reaction notes

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