Sodium sulfate decahydrate → (E)-7'-bromo-4'-fluoro-2'-methoxy-6,7-dihydro-2H-spiro[[1,4]oxazepine-3,9'-xanthen]-5-amine

HRID 529399Notes

Reaction equation

HRID 529399 reaction equation
[NH2:1][C:2]1([CH2:20][O:21][CH2:22][CH2:23][C:24]#[N:25])[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.C[Al](C)C.O.O.O.O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Na+].[Na+]>C1(C)C=CC=CC=1.CCOC(C)=O>[Br:19][C:5]1[CH:4]=[C:3]2[C:8]([O:9][C:10]3[C:11]([F:18])=[CH:12][C:13]([O:16][CH3:17])=[CH:14][C:15]=3[C:2]32[CH2:20][O:21][CH2:22][CH2:23][C:24]([NH2:25])=[N:1]3)=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 62649Sodium sulfate decahydrateHCID 16682925TrimethylaluminumHCID 682794503-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)propanenitrile

Product 1

HCID 68279914(E)-7'-bromo-4'-fluoro-2'-methoxy-6,7-dihydro-2H-spiro[[1,4]oxazepine-3,9'-xanthen]-5-amine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A 250-mL round-bottom flask was charged with 3-((9-amino-7-bromo-4-fluoro-2-methoxy-9H-xanthen-9-yl)methoxy)propanenitrile (2.78 g, 6.83 mmol) and toluene (45.5 mL) to give a pale-green solution. Trimethylaluminum (7.17 mL of a 2M solution in toluene, 14.34 mmol) was added, and a reflux condenser was attached. After stirring for 1 min, the flask was heated to 90° C. for 1 h. After this time, the mixture was cooled to RT. Sodium sulfate decahydrate (3.4 g) was added slowly over 5 min, and the mixture was stirred overnight. In the morning, the mixture was diluted with EtOAc (50 mL) and filtered through celite. The filter pad was washed with EtOAc (3×50 mL). The combined filtrates were concentrated to give a pale-yellow solid. The crude product was purified by chromatography on silica gel (0-10% MeOH/DCM) to give (E)-7′-bromo-4′-fluoro-2′-methoxy-6,7-dihydro-2H-spiro[[1,4]oxazepine-3,9′-xanthen]-5-amine as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=7.53 (d, J=2.4 Hz, 1 H), 7.47 (dd, J=2.5, 8.6 Hz, 1 H), 7.18 (d, J=8.6 Hz, 1 H), 6.95 (dd, J=2.9, 12.3 Hz, 1 H), 6.69 (dd, J=1.5, 2.9 Hz, 1 H), 6.15 (br. s., 2 H), 3.83-3.69 (m, 5 H), 3.64-3.45 (m, 2 H), 3.00-2.74 (m, 2 H). MS m/z=411.0. Calc'd for C18H17BrFN2O3: 407.1.

Workup

  1. customto give a pale-green solution
  2. customa reflux condenser was attached
  3. temperatureAfter this time, the mixture was cooled to RT
  4. stirringthe mixture was stirred overnight
  5. filtrationfiltered through celite
  6. washThe filter pad was washed with EtOAc (3×50 mL)
  7. concentrationThe combined filtrates were concentrated
  8. customto give a pale-yellow solid
  9. customThe crude product was purified by chromatography on silica gel (0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-cfa756dbcadc4ab7a1ef6e3f48c7255f
Source dataset
uspto-grants-2016_05
Patent number
US09346827B2

Reaction notes

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