Methanol → HCID 71761625, compound

HRID 1486962Notes

Reaction equation

HRID 1486962 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH: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)=[CH:4][CH:3]=1.CO.B(F)(F)F.[CH2:36](N(CC)CC)C>ClCCl>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([O:29][CH3:36])[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

Participants

6

Reactant 4

HCID 887MethanolHCID 6356Boron trifluorideHCID 8471TriethylamineHCID 545795431H-Pyrido[3',4':4,5]pyrrolo[1,2,3-de]quinoxaline-8(7H)-butanol, α-(4-fluorophenyl)-2,3,6b,9,10,10a-hexahydro-3-methyl-, (6bR,10aS)-

Product 1

HCID 71761625HCID 71761625, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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-ol (225 mg, 0.57 mmol) in anhydrous dichloromethane (3 mL) is added anhydrous methanol (100 μL, 2.28 mmol), and then BF3.OEt (300 μL, 2.28 mmol, 1.0 M in THF) is added dropwise at room temperature. The reaction mixture is stirred at room temperature overnight, and then poured into ice water. After the mixture is basified with triethylamine, the organic phase is separated and dried over MgSO4, and then evaporated to dryness under reduced pressure. The obtained residue is purified with a semi-preparative HPLC system to give 80 mg of pure product as a brown oil. 1H NMR (500 MHz, DMSO-d6) δ 7.31 (ddd, J=8.6, 5.6, 1.2 Hz, 2H), 7.18 (t, J=8.7 Hz, 2H), 6.50 (td, J=7.6, 1.3 Hz, 1H), 6.39 (d, J=7.3 Hz, 1H), 6.32 (d, J=7.9 Hz, 1H), 4.15 (td, J=6.5, 3.5 Hz, 1H), 3.49-3.37 (m, 1H), 3.31-3.22 (m, 3H), 3.15-3.04 (m, 4H), 3.02-2.91 (m, 1H), 2.77 (s, 3H), 2.70-2.61 (m, 2H), 2.29-2.11 (m, 2H), 2.09-1.97 (m, 1H), 1.92-1.81 (m, 1H), 1.78-1.63 (m, 3H), 1.60-1.49 (m, 1H), 1.49-1.37 (m, 1H), 1.37-1.22 (m, 1H). MS (ESI) m/z 410.6 [M+H]+.

Workup

  1. additionOEt (300 μL, 2.28 mmol, 1.0 M in THF) is added dropwise at room temperature
  2. customthe organic phase is separated
  3. dry with materialdried over MgSO4
  4. customevaporated to dryness under reduced pressure
  5. customThe obtained residue is purified with a semi-preparative HPLC system

Sources & evidence

ORD record
ord-9721f063b2104ab9ba9988dd0072c1b5
Source dataset
uspto-grants-2016_08
Patent number
US09428506B2

Reaction notes

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