Morpholine → 9-Bromo-4-morpholin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

HRID 575101Notes

Reaction equation

HRID 575101 reaction equation
[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[CH:8](Br)[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4].[NH:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1>C1COCC1.CCCCCC>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]2[CH:8]([N:21]3[CH2:26][CH2:25][O:24][CH2:23][CH2:22]3)[CH2:9][O:10][C:11]3[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][C:12]=3[C:13]=2[N:14]=1)=[O:4]

Participants

5

Reactant 2

HCID 8083MorpholineHCID 866930844,9-Dibromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester

Product 1

HCID 866931349-Bromo-4-morpholin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl esterYield 75%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 4,9-Dibromo-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (400 mg, 0.954 mmol) in THF (6 mL) was added morpholine (416 mg, 4.775 mmol). The reaction mixture was stirred at 60° C. for 5 h. Then the mixture was cooled to room temperature and partitioned between EtOAc and H2O, and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo to afford crude product as yellow oil. The oily product was stirred in n-Hexane (6 mL) at room temperature for 0.5 h and then filtered to afford compound 9-Bromo-4-morpholin-4-yl-4,5-dihydro-6-oxa-3-thia-1-aza-benzo[e]azulene-2-carboxylic acid methyl ester (300 mg, 75%) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 8.39 (d, J=2.6 Hz, 1H), 7.48 (dd, J1=8.6 Hz, J2=2.6 Hz, 1H), 7.13 (d, J1=8.64 Hz, 1H), 4.55 (dd, J1=12.08 Hz, J2=3.32 Hz, 1H), 4.40 (dd, J1=6.6 Hz, J2=3.2 Hz, 1H), 4.31 (m, 1H); 3.94 (s, 31-1) 3.56 (m, 4H); 2.68 (m, 4H); LC-MS (ESI & APCI): 427.2 (M+2).

Workup

  1. temperatureThen the mixture was cooled to room temperature
  2. custompartitioned between EtOAc and H2O
  3. extractionthe aqueous layer was extracted with EtOAc (2×20 mL)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto afford crude product as yellow oil
  9. filtrationfiltered

Sources & evidence

ORD record
ord-9509d93695c64b7784c3ba8a53670a6e
Source dataset
uspto-grants-2015_05
Patent number
US09034866B2

Reaction notes

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