N-(tert-butoxycarbonyl)glycine → Methyl 1-(2-(tert-butoxycarbonylamino)acetyl)-4-(hydroxymethyl)piperidine-4-carboxylate

HRID 655968Notes

Reaction equation

HRID 655968 reaction equation
[NH:1]([C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH2:2][C:3]([OH:5])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[OH:37][CH2:38][C:39]1([C:45]([O:47][CH3:48])=[O:46])[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:9]([O:8][C:6]([NH:1][CH2:2][C:3]([N:42]1[CH2:43][CH2:44][C:39]([CH2:38][OH:37])([C:45]([O:47][CH3:48])=[O:46])[CH2:40][CH2:41]1)=[O:5])=[O:7])([CH3:12])([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57920285Methyl 4-(hydroxymethyl)piperidine-4-carboxylate

Product 1

HCID 57920289Methyl 1-(2-(tert-butoxycarbonylamino)acetyl)-4-(hydroxymethyl)piperidine-4-carboxylateYield 98.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Boc-Gly-OH (331 mg, 1.89 mmol, 1.1 equiv.) in DMF (1 mL) was added HBTU (718 mg, 1.89 mmol, 1.1 equiv.), followed by addition of methyl 4-(hydroxymethyl)piperidine-4-carboxylate (1.72 mmol, 1 equiv.) and DIEA (749 μL, 4.30 mmol, 2.5 equiv.) at rt. The reaction mixture was stirred for 1 h. The mixture was partitioned between EtOAc and H2O. The organic layer was washed by saturated NaHCO3, water and brine, dried over Na2SO4, and concentrated. The resulting residue was purified by column chromatography to give methyl 1-(2-(tert-butoxycarbonylamino)acetyl)-4-(hydroxymethyl)piperidine-4-carboxylate (560 mg, 98%, two steps). LRMS (M-Boc+H+) m/z 231.1.

Workup

  1. customThe mixture was partitioned between EtOAc and H2O
  2. washThe organic layer was washed by saturated NaHCO3, water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-d8ccd7a71e7b4dd18be5d717a24492a3
Source dataset
uspto-grants-2011_12
Patent number
US08071625B2

Reaction notes

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