Morpholine → HCID 51348415, compound

HRID 1958626Notes

Reaction equation

HRID 1958626 reaction equation
[C:1](=[O:37])([O:6][C:7]([CH3:36])([CH3:35])[CH2:8][NH:9][C:10]([NH:12][C@H:13]([CH:32]([CH3:34])[CH3:33])[C:14]([N:16]1[CH2:21][CH2:20][C@@:19]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)([OH:22])[C:18]([CH3:31])([CH3:30])[CH2:17]1)=[O:15])=[O:11])[O:2][CH2:3][CH2:4]Br.C([O-])([O-])=O.[K+].[K+].[NH:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1>CN(C=O)C>[C:1](=[O:37])([O:2][CH2:3][CH2:4][N:44]1[CH2:49][CH2:48][O:47][CH2:46][CH2:45]1)[O:6][C:7]([CH3:36])([CH3:35])[CH2:8][NH:9][C:10]([NH:12][C@H:13]([CH:32]([CH3:34])[CH3:33])[C:14]([N:16]1[CH2:21][CH2:20][C@@:19]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)([OH:22])[C:18]([CH3:31])([CH3:30])[CH2:17]1)=[O:15])=[O:11]

Participants

5

Reactant 3

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 58215042HCID 58215042, compound

Product 1

HCID 51348415HCID 51348415, compoundYield 79%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-bromoethyl 1-(3-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)ureido)-2-methylpropan-2-yl carbonate (780 mg, 1.289 mmol) and K2CO3 (356 mg, 2.58 mmol) in DMF (3 mL) was added morpholine and the reaction was stirred at rt overnight. After drying the crude product overnight under high vacuum, the residual glass was purified via column chromatography (50% EA/hep to 100% EA to 5% MeOH/EA) to furnish 1-(3-((R)-1-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-3-methyl-1-oxobutan-2-yl)ureido)-2-methylpropan-2-yl 2-morpholinoethyl carbonate (620 mg, 1.014 mmol, 79% yield) as a foam. 1H NMR (CDCl3, 400 MHz, rotameric) δ 7.40-7.24 (m, 4H), 5.44 (dd, J=21.9, 8.8 Hz, 1H), 5.13 (dt, J=21.1, 5.7 Hz, 1H), 4.82 (m, 1H), 4.65 (br d, 0.5H), 4.20 (t, J=6.2 Hz, 2H), 3.95 (m, 0.5H), 3.71 (t, J=4.8 Hz, 4H), 3.58 (m, 1H), 3.43 (m, 3H), 3.15 (dt, J=13.1, 2.6 Hz, 0.5H), 3.05 (d, J=12.7 Hz, 0.5H), 2.64 (t, J=5.7 Hz, 2H), 2.51 (t, J=4.4 Hz, 4H), 1.96 (m, 1H), 1.54 (m, 1H), 1.47-1.43 (m, 6H), 1.06 (d, J=6.6 Hz, 1.5H), 0.97-0.76 (m, 10.5H). HPLC Purity: >99%, rt 3.23 min (Chromalith Speedrod, C18, 4.6×50 mm, 10% MeOH/water to 90% MeOH/water with 0.2% H3PO4, 4 min gradient, 4 mL/min) LCMS: 611.38 (M+)

Workup

  1. dry with materialAfter drying the crude product overnight under high vacuum
  2. customthe residual glass was purified via column chromatography (50% EA/hep to 100% EA to 5% MeOH/EA)

Sources & evidence

ORD record
ord-cf6d76ea1f834838805d07d03578f207
Source dataset
uspto-grants-2013_04
Patent number
US08410139B2

Reaction notes

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