3-Fluorobenzylamine → Tert-butyl 2-(4-(3-fluoro-2-methylbenzylcarbamoyl)-4-(hydroxymethyl)piperidin-1-yl)-2-oxoethylcarbamate

HRID 655970Notes

Reaction equation

HRID 655970 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([N:12]1[CH2:17][CH2:16][C:15]([CH2:21][OH:22])([C:18]([OH:20])=O)[CH2:14][CH2:13]1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:23]N(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[F:47][C:48]1[CH:49]=[C:50]([CH:53]=[CH:54][CH:55]=1)[CH2:51][NH2:52].CCN(C(C)C)C(C)C>CN(C=O)C>[F:47][C:48]1[C:49]([CH3:23])=[C:50]([CH:53]=[CH:54][CH:55]=1)[CH2:51][NH:52][C:18]([C:15]1([CH2:21][OH:22])[CH2:14][CH2:13][N:12]([C:10](=[O:11])[CH2:9][NH:8][C:6](=[O:7])[O:5][C:1]([CH3:3])([CH3:4])[CH3:2])[CH2:17][CH2:16]1)=[O:20]

Participants

6

Reactant 4

HCID 668533-FluorobenzylamineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 579202801-(2-(Tert-butoxycarbonylamino)acetyl)-4-(hydroxymethyl)piperidine-4-carboxylic acid

Product 1

HCID 59778520Tert-butyl 2-(4-(3-fluoro-2-methylbenzylcarbamoyl)-4-(hydroxymethyl)piperidin-1-yl)-2-oxoethylcarbamateYield 111.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of crude 1-(2-(tert-butoxycarbonylamino)acetyl)-4-(hydroxymethyl)piperidine-4-carboxylic acid (120 mg, ˜0.379 mmol, 1.0 equiv) in DMF (30 mL) were added HBTU (144 mg, 0.379 mmol, 1.0 equiv.), 2-methyl, 3-fluorobenzylamine (53 mg, 0.379 mmol, 1.0 equiv.) and DIEA (132 μL, 0.758 mmol, 2.0 equiv.). The reaction mixture was stirred overnight at rt. The mixture was partitioned between EtOAc and H2O. The organic layer was washed by 1 N HCl, Saturated NaHCO3, water and brine, dried over Na2SO4, and concentrated to dryness to give tert-butyl 2-(4-(3-fluoro-2-methylbenzylcarbamoyl)-4-(hydroxymethyl)piperidin-1-yl)-2-oxoethylcarbamate (185 mg), which was used without further purification. LRMS (M+H+) m/z 439.1.

Workup

  1. customThe mixture was partitioned between EtOAc and H2O
  2. washThe organic layer was washed by 1 N HCl, Saturated NaHCO3, water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-987870ed313d4dc68a56f55ea39004ef
Source dataset
uspto-grants-2011_12
Patent number
US08071625B2

Reaction notes

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