Diethyl Ether → HCID 71816067, compound

HRID 1486961Notes

Reaction equation

HRID 1486961 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:29])[CH2:9][CH2:10][CH2:11][N:12]2[CH2:28][CH2:27][C@@H:15]3[N:16]4[C:25]5[C:24]([C@@H:14]3[CH2:13]2)=[CH:23][CH:22]=[CH:21][C:20]=5[N:19]([CH3:26])[CH2:18][CH2:17]4)=[CH:4][CH:3]=1.[CH3:30][Mg]Br.CCOCC>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([OH:29])([CH2:9][CH2:10][CH2:11][N:12]2[CH2:28][CH2:27][C@@H:15]3[N:16]4[C:25]5[C:24]([C@@H:14]3[CH2:13]2)=[CH:23][CH:22]=[CH:21][C:20]=5[N:19]([CH3:26])[CH2:18][CH2:17]4)[CH3:30])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 3283Diethyl Ether2×HCID 21302490rel-1-(4-Fluorophenyl)-4-[(6bR,10aS)-2,3,6b,9,10,10a-hexahydro-3-methyl-1H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8(7H)-yl]-1-butanoneHCID 178418573HCID 178418573, compound2×HCID 178418689HCID 178418689, compound

Product 1

HCID 71816067HCID 71816067, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(4-fluoro-phenyl)-4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-butan-1-one (99 mg, 0.25 mmol) in THF is added 3.0 M methyl magnesium bromide in ether (0.25 mL, 0.75 mmol) dropwise at 0° C. Upon the completion of the addition of CH3MgBr, the cooling bath is removed and the reaction mixture is stirred at room temperature for 2 hours. Another batch of 3.0 M methyl magnesium bromide in ether (0.25 mL, 0.75 mmol) is added dropwise, and the reaction mixture was stirred at room temperature overnight. The mixture is carefully quenched with water, basified with saturated sodium bicarbonate, and then extracted with methylene chloride four times. The combined organic phase is evaporated to dryness, and the residue is purified on a basic alumina column to give 28 mg of pure product as a white solid. 1H NMR (500 MHz, Chloroform-d) δ 8.22 (br, 1H), 7.58-7.37 (m, 2H), 7.07 (t, J=8.5 Hz, 1H), 7.01 (t, J=8.7 Hz, 1H), 6.65 (dt, J=10.6, 7.7 Hz, 1H), 6.57-6.29 (m, 2H), 3.59 (td, J=11.1, 3.0 Hz, 1H), 3.37-3.12 (m, 4H), 3.00-2.65 (m, 5H), 2.55-2.13 (m, 5H), 2.12-1.78 (m, 4H), 1.69-1.30 (m, 5H). MS (ESI) m/z 410.2 [M+H]+.

Workup

  1. customthe cooling bath is removed
  2. stirringthe reaction mixture was stirred at room temperature overnight
  3. customThe mixture is carefully quenched with water
  4. extractionextracted with methylene chloride four times
  5. customThe combined organic phase is evaporated to dryness
  6. customthe residue is purified on a basic alumina column

Sources & evidence

ORD record
ord-e4b3376d38bc46778ac1e5aa61c3f8dc
Source dataset
uspto-grants-2016_08
Patent number
US09428506B2

Reaction notes

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