Bromoacetonitrile → (R)-tert-butyl 3-((R)-(3-chlorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate

HRID 452001Notes

Reaction equation

HRID 452001 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([OH:22])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Na+].Br[CH2:26][C:27]#[N:28]>CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([C@H:8]([O:22][CH2:26][C:27]#[N:28])[C@@H:9]2[CH2:14][CH2:13][CH2:12][N:11]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:10]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 445550221-Piperidinecarboxylic acid, 3-[(R)-(3-chlorophenyl)hydroxymethyl]-, 1,1-dimethylethyl ester, (3R)-

Product 1

HCID 67364989(R)-tert-butyl 3-((R)-(3-chlorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-tert-butyl 3-((R)-(3-chlorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (32.5 g, 0.1 mol) in MeCN (325 mL), NaH (12 g, 0.3 mol) was added at 0° C. The mixture was stirred for 1 hr at rt. The mixture was cooled to −40° C., then bromoacetonitrile (35.7 g, 0.3 mol) was added in portions. The mixture was stirred for 0.5 hr at −20° C. After the reaction was complete it was quenched with sat. NH4Cl. The mixture was extracted with CH2Cl2. The organic layer was dried over Na2SO4, concentrated. Crude (R)-tert-butyl 3-((R)-(3-chlorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate was used for the next step without further purification.

Workup

  1. temperatureThe mixture was cooled to −40° C.
  2. stirringThe mixture was stirred for 0.5 hr at −20° C
  3. customwas quenched with sat. NH4Cl
  4. extractionThe mixture was extracted with CH2Cl2
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated
  7. customCrude (R)-tert-butyl 3-((R)-(3-chlorophenyl)(cyanomethoxy)methyl)piperidine-1-carboxylate was used for the next step without further purification

Sources & evidence

ORD record
ord-683c65ce35ba4bf894b47ebf1e46ced0
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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