Diisopropylethylamine → Biphenyl-2-ylcarbamic Acid 1-(2-{[3-(9H-Fluoren-9-ylmethoxycarbonylamino)propyl]methylcarbamoyl}ethyl)piperidin-4-yl Ester

HRID 1039825Notes

Reaction equation

HRID 1039825 reaction equation
[C:1]1([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]([O:10][CH:11]1[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][C:19](O)=[O:20])[CH2:13][CH2:12]1)=[O:9].C(N(CC)C(C)C)(C)C.[I-].ClC1C=CC=C[N+]=1C.Cl.[CH:47]1[C:59]2[CH:58]([CH2:60][O:61][C:62](=[O:69])[NH:63][CH2:64][CH2:65][CH2:66][NH:67][CH3:68])[C:57]3[C:52](=[CH:53][CH:54]=[CH:55][CH:56]=3)[C:51]=2[CH:50]=[CH:49][CH:48]=1>CN(C=O)C>[CH:56]1[C:57]2[CH:58]([CH2:60][O:61][C:62]([NH:63][CH2:64][CH2:65][CH2:66][N:67]([CH3:68])[C:19]([CH2:18][CH2:17][N:14]3[CH2:13][CH2:12][CH:11]([O:10][C:8](=[O:9])[NH:7][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][C:1]=4[C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH2:16][CH2:15]3)=[O:20])=[O:69])[C:59]3[C:51](=[CH:50][CH:49]=[CH:48][CH:47]=3)[C:52]=2[CH:53]=[CH:54][CH:55]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 1670692-Chloro-1-methylpyridinium iodideHCID 218806073-[4-(Biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]propionic AcidHCID 66770088N-Fmoc-3-methylamino propylamine HCl

Product 1

HCID 66770111Biphenyl-2-ylcarbamic Acid 1-(2-{[3-(9H-Fluoren-9-ylmethoxycarbonylamino)propyl]methylcarbamoyl}ethyl)piperidin-4-yl EsterYield 99.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 3-[4-(biphenyl-2-ylcarbamoyloxy)piperidin-1-yl]-propionic acid (2.8 g, 7.6 mmol) and N,N-diisopropylethylamine (2.6 mL, 15 mmol) in DMF (31 mL) was added 2-chloro-1-methylpyridinium iodide (3.9 g, 15 mmol). Once the solids had dissolved, (3-methylaminopropyl)carbamic acid 9H-fluoren-9-ylmethyl ester hydrochloride salt (2.63 g, 7.58 mmol) was added and the resulting mixture was stirred at room temperature until essentially complete by HPLC and LCMS. The mixture was then concentrated under reduced pressure to remove most of the DMF and the residue was dissolved in DCM (30 mL). This mixture was washed with water (3×20 mL) and brine (3×20 mL), dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-20% MeOH in DCM) to give the title compound (5.0 g, 97% yield) as a white solid.

Workup

  1. dissolutionOnce the solids had dissolved
  2. concentrationThe mixture was then concentrated under reduced pressure
  3. customto remove most of the DMF
  4. dissolutionthe residue was dissolved in DCM (30 mL)
  5. washThis mixture was washed with water (3×20 mL) and brine (3×20 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel flash chromatography (0-20% MeOH in DCM)

Sources & evidence

ORD record
ord-acad709f1f704dbc9fea02ed6ea896e5
Source dataset
uspto-grants-2013_10
Patent number
US08551978B2

Reaction notes

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