Tetrahydrofuran → Methyl 2-(1-methyl-3-(3(4-octylphenyl)ureido)piperidin-3-yl)acetate

HRID 1192896Notes

Reaction equation

HRID 1192896 reaction equation
[NH2:1][C:2]1([CH2:9][C:10]([O:12][CH3:13])=[O:11])[CH2:7][CH2:6][CH2:5][N:4]([CH3:8])[CH2:3]1.CC[N:16]([CH:20](C)C)[CH:17]([CH3:19])[CH3:18].ClC(Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl.[CH2:35](NC1C=CC=CC=1)[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42].[CH2:50]1[CH2:54]OC[CH2:51]1>>[CH3:8][N:4]1[CH2:5][CH2:6][CH2:7][C:2]([CH2:9][C:10]([O:12][CH3:13])=[O:11])([NH:1][C:20]([NH:16][C:17]2[CH:18]=[CH:54][C:50]([CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[CH:51][CH:19]=2)=[O:26])[CH2:3]1

Participants

6

Reactant 5

HCID 8028TetrahydrofuranHCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 137788N-OctylanilineHCID 66864584Methyl 2-(3-amino-1-methylpiperidin-3-yl)acetate

Product 1

HCID 66865087Methyl 2-(1-methyl-3-(3(4-octylphenyl)ureido)piperidin-3-yl)acetateYield 56%

Conditions

Temperature
0 °C

Procedure

A solution of methyl 2-(3-amino-1-methylpiperidin-3-yl)acetate (235 mg, 1.3 mmol) in and THF (10 mL), at 0° C., under N2, was treated with DIPEA (0.22 mL, 1.3 mmol) and triphosgene (133 mg, 0.45 mmol), in one portion. The reaction was stirred at 0° C. for a few min and then at rt for 110 min. The reaction was cooled to 0° C., treated with the N-octylaniline (0.29 mL, 1.3 mmol) followed by DIPEA (0.22 mL, 1.3 mmol). After 5 min the cooling bath was removed and the reaction was diluted with and THF (10 mL). Stirring was continued at rt overnight. The reaction was then concentrated under reduced pressure and purified by flash chromatography on silica gel using 0-12% MeOH/DCM as the eluent to isolate the title product as a white solid (0.296 g, 56%). 1H NMR (400 MHz, CD3OD) δ ppm 7.20 (d, J=8.59 Hz, 2 H), 7.05 (d, J=8.34 Hz, 2 H), 3.64 (s, 3 H), 2.89 (m, 2 H), 2.76 (br. s., 1 H), 2.54 (t, J=7.58 Hz, 2 H), 2.27 (s, 3 H), 1.97-2.23 (m, 3 H), 1.67-1.85 (m, 1 H), 1.50-1.66 (m, 3 H), 1.30 (d, J=7.33 Hz, 12 H), 0.89 (t, J=6.82 Hz, 3 H). MS ESI [M+H]+, calcd for [C24H39N3O3+H] 418.59 found m/z 418.3 (100).

Workup

  1. temperatureThe reaction was cooled to 0° C.
  2. customAfter 5 min the cooling bath was removed
  3. additionthe reaction was diluted with and THF (10 mL)
  4. stirringStirring
  5. waitwas continued at rt overnight
  6. concentrationThe reaction was then concentrated under reduced pressure
  7. custompurified by flash chromatography on silica gel using 0-12% MeOH/DCM as the eluent

Sources & evidence

ORD record
ord-3e3f6a9ebda14159b37de2c215d99a4c
Source dataset
uspto-grants-2014_03
Patent number
US08680282B2

Reaction notes

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