Boron trifluoride etherate → Benzyl 4-chloro-3-(diethoxyphosphorylamino)piperidine-1-carboxylate

HRID 73563Notes

Reaction equation

HRID 73563 reaction equation
[CH2:1]([O:3][P:4]([N:9]1[CH:15]2[CH:10]1[CH2:11][CH2:12][N:13]([C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[CH2:14]2)([O:6][CH2:7][CH3:8])=[O:5])[CH3:2].[ClH:26].C(N(CC)CC)C.B(F)(F)F.CCOCC>C(Cl)Cl>[Cl:26][CH:10]1[CH2:11][CH2:12][N:13]([C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH2:14][CH:15]1[NH:9][P:4]([O:6][CH2:7][CH3:8])([O:3][CH2:1][CH3:2])=[O:5]

Participants

5

Reactant 3

HCID 8000Boron trifluoride etherateHCID 11130Triethylamine hydrochlorideHCID 59455678Benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate

Product 1

HCID 67500461Benzyl 4-chloro-3-(diethoxyphosphorylamino)piperidine-1-carboxylateYield 89%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of benzyl 7-(diethoxyphosphoryl)-3,7-diazabicyclo[4.1.0]heptane-3-carboxylate (1.0 equiv.) and triethyl amine hydrochloride (4 equiv.) in DCM (0.1M) was added BF3.OEt2 (2.0 equiv.) and the reaction was allowed to stir at room temperature for 2 h under a nitrogen atmosphere. The solution was then quenched with water and extracted with DCM. The crude product was purified via silica gel column chromatography (ISCO eluting with EtOAc and Hexanes 50% to 100% EtOAc) to yield benzyl 4-chloro-3-(diethoxyphosphorylamino)piperidine-1-carboxylate in 89% yield. LCMS (m/z): 405.1 (MH+), Rt=2.73 min.

Workup

  1. customThe solution was then quenched with water
  2. extractionextracted with DCM
  3. customThe crude product was purified via silica gel column chromatography (ISCO eluting with EtOAc and Hexanes 50% to 100% EtOAc)

Sources & evidence

ORD record
ord-65a2bd7f7551455a8cb6f9c705a5269e
Source dataset
uspto-grants-2014_09
Patent number
US08829193B2

Reaction notes

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