2,6-Lutidine → (R)-Ethyl 4-(4-((tert-butyldimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoate

HRID 1476265Notes

Reaction equation

HRID 1476265 reaction equation
N1C(C)=CC=CC=1C.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C@H:22]([OH:40])[CH:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:39]=[CH:38][C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:31][CH:30]=3)[CH2:25][CH2:24]2)=[CH:12][CH:11]=1.FC(F)(F)S(O[Si:47]([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:49])[CH3:48])(=O)=O>C(Cl)Cl>[Si:47]([O:40][C@@H:22]([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[C:13]1[CH:12]=[CH:11][C:10]([Cl:9])=[CH:15][CH:14]=1)[CH:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:30]=[CH:31][C:32]([C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:38][CH:39]=2)[CH2:25][CH2:24]1)([C:50]([CH3:53])([CH3:52])[CH3:51])([CH3:49])[CH3:48]

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 56650671(R)-ethyl 4-(4-((4'-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate

Product 1

HCID 58080191(R)-Ethyl 4-(4-((tert-butyldimethylsilyloxy)(4'-chlorobiphenyl-2-yl)methyl)piperidin-1-yl)benzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2,6-Lutidine (1.128 ml, 9.68 mmol) was added to a solution of (R)-ethyl 4-(4-((4′-chlorobiphenyl-2-yl)(hydroxy)methyl)piperidin-1-yl)benzoate (INTERMEDIATE 11A (First Eluting Compound), 1.74 g, 3.87 mmol) in DCM (10 ml) at 0° C. tert-Butyldimethylsilyl trifluoromethanesulfonate (1.3 ml, 5.81 mmol) was added dropwise via syringe at 0° C. and the resulting mixture was allowed to warm up to room temperature for 10 minutes. Evaporation of the volatiles under reduced pressure gave a residue, which was purified by column chromatography (ISCO, 80 g silicon column, eluting with 0→10% EtOAc/hexanes) to give the title product (2.1 g, yield: almost quantitative).

Workup

  1. additionwas added dropwise via syringe at 0° C.
  2. customEvaporation of the volatiles under reduced pressure
  3. customgave a residue, which
  4. customwas purified by column chromatography (ISCO, 80 g silicon column, eluting with 0→10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-827d4d23eb8c4335b56c662fbde8f13b
Source dataset
uspto-grants-2015_04
Patent number
US09018381B2

Reaction notes

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