Sodium Carbonate → (R)-2'-bromo-7'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

HRID 455715Notes

Reaction equation

HRID 455715 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[F:7][C:8]1[CH:13]=[C:12](B(O)O)[CH:11]=[CH:10][N:9]=1.[Br:17][C:18]1[CH:31]=[CH:30][C:29]2[O:28][C:27]3[C:22](=[CH:23][C:24](I)=[CH:25][CH:26]=3)[C@@:21]3([N:37]=[C:36]([NH2:38])[CH2:35][O:34][CH2:33]3)[C:20]=2[CH:19]=1>COCCOC.O.[Cl-].[Na+].O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Br:17][C:18]1[CH:31]=[CH:30][C:29]2[O:28][C:27]3[C:22](=[CH:23][C:24]([C:12]4[CH:11]=[CH:10][N:9]=[C:8]([F:7])[CH:13]=4)=[CH:25][CH:26]=3)[C@@:21]3([N:37]=[C:36]([NH2:38])[CH2:35][O:34][CH2:33]3)[C:20]=2[CH:19]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27833962-Fluoropyridine-4-boronic acidHCID 58465890(S)-2'-bromo-7'-iodo-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

Product 1

HCID 67438537(R)-2'-bromo-7'-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

In a microwave vial, sodium carbonate (0.094 g, 0.885 mmol), 2-fluoropyridin-4-ylboronic acid (0.048 g, 0.339 mmol), Pd(PPh3)4 (0.034 g, 0.030 mmol), and (S)-2′-bromo-7′-iodo-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (0.139 g, 0.295 mmol) were suspended in DME (2.5 mL) and water (0.5 mL). Argon gas was blown through the vessel which was sealed and heated in an 80° C. oil bath. After 6 h, the reaction mixture was diluted with brine (10 mL) and the aqueous phase was extracted with 7.5% MeOH-dcm (3×25 mL). The organics were combined, washed with dilute brine (5 mL), dried over sodium sulfate and concentrated. The material was purified through silica gel (33 mL) using 3.5 to 4.5 to 7% MeOH-DCM to afford (R)-2′-bromo-7′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine

Workup

  1. customwas sealed
  2. extractionthe aqueous phase was extracted with 7.5% MeOH-dcm (3×25 mL)
  3. washwashed with dilute brine (5 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated
  6. customThe material was purified through silica gel (33 mL)

Sources & evidence

ORD record
ord-0d65ec2769d648b982fbfbe716c07e1c
Source dataset
uspto-grants-2013_07
Patent number
US08497264B2

Reaction notes

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