Chloroacetyl chloride → Tert-butyl 4-[benzyl(chloroacetyl)amino]-3-hydroxypiperidine-1-carboxylate

HRID 81113Notes

Reaction equation

HRID 81113 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:10]([OH:22])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(OC(N1CCC(O)C(NCC2C=CC=CC=2)C1)=O)(C)(C)C.C(N(CC)CC)C.[Cl:52][CH2:53][C:54](Cl)=[O:55]>C(Cl)Cl>[CH2:15]([N:14]([C:54](=[O:55])[CH2:53][Cl:52])[CH:11]1[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:9][CH:10]1[OH:22])[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1

Participants

6

Reactant 4

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 57452747Tert-butyl-4-(benzylamino)-3-hydroxypiperidine-1-carboxylateHCID 57452748Tert-butyl-3-(benzylamino)-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 86724481Tert-butyl 4-[benzyl(chloroacetyl)amino]-3-hydroxypiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl-4-(benzylamino)-3-hydroxypiperidine-1-carboxylate and tert-butyl-3-(benzylamino)-4-hydroxypiperidine-1-carboxylate (153 g, 0.42 mol, crude) and triethylamine (126 g, 1.25 mol) in DCM (800 mL) was added drop wise chloroacetyl chloride (33 g, 0.45 mol) at room temperature. The mixture was stirred at room temperature overnight. The mixture was quenched with water (300 mL) at 0° C., and extracted with DCM (500 mL×3). The organic layer was washed with brine (1 L), dried over sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel chromatography to afford tert-butyl 4-[benzyl(chloroacetyl)amino]-3-hydroxypiperidine-1-carboxylate as a mixture of trans diastereomers which was used directly in the next step.

Workup

  1. customThe mixture was quenched with water (300 mL) at 0° C.
  2. extractionextracted with DCM (500 mL×3)
  3. washThe organic layer was washed with brine (1 L)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ed4cbe847d8e49038c7a5b9a0ad9d8b7
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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