Diisopropylethylamine → HCID 24769023, compound

HRID 2422860Notes

Reaction equation

HRID 2422860 reaction equation
C([O-])(=O)C.[NH4+].C([BH3-])#N.[Na+].[CH3:10][O:11][C:12]1[CH:13]=[C:14]([CH:26]([NH2:28])[CH3:27])[CH:15]=[CH:16][C:17]=1[C:18]1[C:19]([O:24][CH3:25])=[N:20][CH:21]=[CH:22][CH:23]=1.[F:29][C:30]([F:43])([F:42])[O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[S:38](Cl)(=[O:40])=[O:39].C(N(C(C)C)CC)(C)C>CO.ClCCl.CCCCCCC.C(OCC)(=O)C>[CH3:10][O:11][C:12]1[CH:13]=[C:14]([C@H:26]([NH:28][S:38]([C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=2[O:31][C:30]([F:29])([F:42])[F:43])(=[O:40])=[O:39])[CH3:27])[CH:15]=[CH:16][C:17]=1[C:18]1[C:19]([O:24][CH3:25])=[N:20][CH:21]=[CH:22][CH:23]=1

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 517165Ammonium AcetateHCID 27772152-(Trifluoromethoxy)benzene-1-sulfonyl chlorideHCID 5003444Sodium cyanoborohydrideHCID 67243866HCID 67243866, compound

Product 1

HCID 24769023HCID 24769023, compound

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 21899848Ethylacetate heptaneSolvent

Procedure

A mixture of acetovanillone (0.332 g, 2.0 mmol), N-phenyl-bis(trifluoromethane-sulfonimide) (710 mg, 2.0 mmol), potassium carbonate (830 mg, 6.0 mmol) and tetrahydrofuran (3.0 ml) was heated to 120° C. for 6 min in a microwave oven. 2-Methoxypyridine-3-boronic acid (611 mg, 4 mmol), tetrakis(triphenylphosphine)palladium (0) (115 mg, 100 μmol), N-methylpyrrolidinone (1 ml) were then added and the mixture heated in the microwave at 120° C. for 10 min. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase was separated and washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate and the solvent evaporated to give 1-[3-methoxy-4-(2-methoxy-pyridin-3yl)-phenyl]-ethanone in quantitative yield. Reductive amination with ammonium acetate (20 equivalents) in methanol (50 ml) containing sodium cyanoborohydride (1 equivalent) followed by aqueous work-up with saturated aqueous sodium bicarbonate and extraction into ethyl actetate gave, after solvent was evaporated 1-[3-methoxy-4-(2-methoxy-pyridin-3yl)-phenyl]-ethylamine. To 1-[3-methoxy-4-(2-methoxy-pyridin-3yl)-phenyl]-ethylamine was added 2-trifluoromethoxy-benzenesulfonyl chloride (1 equivalent) in dichloromethane, diisopropylethylamine (4 equivalents) and the mixture overnight. The racemic product was isolated by normal phase HPLC on silica gel eluting with heptane/ethyl acetate and the solvent evaporated to give a clear oily solid (72 mg). 1H NMR (400 MHz, CDCl3): δ 8.15 (d, 1H), 7.9 (d, 1H), 7.5 (m, 1H), 7.4 (m, 1H), 7.3-7.2 (m, 2H), 7.05 (d, 1H), 6.9 (m, 1H), 6.75-6.65 (m, 2H), 5.0 (d, 1H), 4.55 (m, 1H), 3.91 (s, 3H), 3.67 (s, 3H), 1.51 (d, 3H) ppm; MS (ESI) m/z: 483.3 [M+1]+. The racemate was resolved by chiral HPLC (CHIRALPAK-AS, eluting with 9:1 isohexane/ethanol) to give the title compound (11 mg) and its enantiomer (11) mg.

Workup

  1. extractionfollowed by aqueous work-up with saturated aqueous sodium bicarbonate and extraction into ethyl actetate
  2. customgave
  3. customafter solvent was evaporated 1-[3-methoxy-4-(2-methoxy-pyridin-3yl)-phenyl]-ethylamine
  4. customthe mixture overnight
  5. customthe solvent evaporated

Sources & evidence

ORD record
ord-24a2a047f9b745caab2270d1a5618e0d
Source dataset
uspto-grants-2011_06
Patent number
US07960365B2

Reaction notes

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