Acrylonitrile → 3-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)propanenitrile

HRID 529398Notes

Reaction equation

HRID 529398 reaction equation
[NH2:1][C:2]1([CH2:20][OH:21])[C:15]2[CH:14]=[C:13]([O:16][CH3:17])[CH:12]=[C:11]([F:18])[C:10]=2[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:19])=[CH:6][CH:7]=2.C1COCC1.[C:27](#[N:30])[CH:28]=[CH2:29].[OH-].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.CCOC(C)=O>[NH2:1][C:2]1([CH2:20][O:21][CH2:29][CH2:28][C:27]#[N:30])[C:15]2[CH:14]=[C:13]([O:16][CH3:17])[CH:12]=[C:11]([F:18])[C:10]=2[O:9][C:8]2[C:3]1=[CH:4][C:5]([Br:19])=[CH:6][CH:7]=2

Participants

7

Reactant 4

HCID 7855AcrylonitrileHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 67383452(9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methanol

Product 1

HCID 682794503-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)propanenitrile

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A 100-mL RBF was charged with (9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methanol (2.318 g, 6.54 mmol), tetrabutylammonium hydrogen sulfate (0.111 g, 0.327 mmol), THF (32.7 mL), and acrylonitrile (2.154 mL, 32.7 mmol) to give a clear solution. NaOH (8.18 mL of a 2N aq. solution, 16.36 mmol) was added, and the resulting mixture was stirred for 1.5 h. The reaction mixture was diluted with EtOAc (70 mL), washed with water (2×50 mL), washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by chromatography on silica gel (0-10% MeOH/DCM) to give 3-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)propanenitrile as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ=7.97 (d, J=2.4 Hz, 1 H), 7.45 (dd, J=2.5, 8.7 Hz, 1 H), 7.19 (dd, J=1.7, 2.9 Hz, 1 H), 7.09 (d, J=8.6 Hz, 1 H), 6.96-6.89 (m, 1 H), 3.77 (s, 3 H), 3.64 (t, J=6.0 Hz, 1 H), 3.54-3.42 (m, J=2.1 Hz, 3 H), 3.38-3.23 (m, 2 H), 2.85-2.74 (m, 2 H).

Workup

  1. customto give a clear solution
  2. washwashed with water (2×50 mL)
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by chromatography on silica gel (0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-dd320f725fc944fe962f5451552166b4
Source dataset
uspto-grants-2016_05
Patent number
US09346827B2

Reaction notes

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