Diisopropylethylamine → 1-(6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthren-3-ylmethyl)-piperidin-4-yl-carbamic acid tert-butyl ester

HRID 633816Notes

Reaction equation

HRID 633816 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].Br[CH2:16][CH:17]1[CH2:30][C:29]2[C:28]3[C:23](=[CH:24][CH:25]=[C:26]([O:31][CH3:32])N=3)[N:22]=[CH:21][C:20]=2[O:19][CH2:18]1.[CH:33](N(CC)C(C)C)(C)C>CN(C)C=O>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:16][CH:17]2[CH2:30][C:29]3[C:28]4[C:23](=[CH:24][CH:25]=[C:26]([O:31][CH3:32])[CH:33]=4)[N:22]=[CH:21][C:20]=3[O:19][CH2:18]2)[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 7238334-(N-Boc-amino)piperidineHCID 867306953-bromomethyl-6-methoxy-3,4-dihydro-2H-1-oxa-5,9-diaza-phenanthrene

Product 1

HCID 711180001-(6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthren-3-ylmethyl)-piperidin-4-yl-carbamic acid tert-butyl esterYield 87.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Piperidin-4-yl-carbamic acid tert-butyl ester (301 mg, 1.46 mmol, 1.0 eq) is added at room temperature to a stirred solution of 3-bromomethyl-6-methoxy-3,4-dihydro-2H-1-oxa-5,9-diaza-phenanthrene (500 mg, 1.46 mmol, 1.0 eq) in N,N-dimethylformamide (15 mL), followed by N,N-diisopropylethylamine (281 μL, 1.61 mmol, 1.1 eq). After 24 hours stirring at 80° C., solvent is removed and the residue is extracted with dichloromethane (3×30 mL) and water (30 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a residue that is purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 1:3:0 to 0:1:0 to 0:9:1, v/v/v) to afford [1-(6-methoxy-3,4-dihydro-2H-1-oxa-9-aza-phenanthren-3-ylmethyl)-piperidin-4-yl-carbamic acid tert-butyl ester as a brown viscous oil (544 mg, 74% yield).

Workup

  1. customsolvent is removed
  2. extractionthe residue is extracted with dichloromethane (3×30 mL) and water (30 mL)
  3. dry with materialThe combined organic layers are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a residue that
  7. customis purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 1:3:0 to 0:1:0 to 0:9:1, v/v/v)

Sources & evidence

ORD record
ord-07ec77c3344f40a6add23da92529c7dd
Source dataset
uspto-grants-2016_04
Patent number
US09321788B2

Reaction notes

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