Ammonium Hydroxide → HCID 67353972, compound

HRID 1670831Notes

Reaction equation

HRID 1670831 reaction equation
C[O:2][C:3](=O)[CH:4]([N:8]1[CH2:13][CH2:12][C:11]([F:15])([F:14])[CH2:10][CH2:9]1)[CH2:5][C:6]#[N:7].[BH4-].[Na+].[OH-].[NH4+]>C1COCC1.O.O.O.O.O.O.O.[Co](Cl)Cl>[F:14][C:11]1([F:15])[CH2:12][CH2:13][N:8]([CH:4]2[CH2:5][CH2:6][NH:7][C:3]2=[O:2])[CH2:9][CH2:10]1

Participants

7

Reactant 3

HCID 14923Ammonium HydroxideHCID 4311764Sodium borohydrideHCID 67354460HCID 67354460, compound

Product 1

HCID 67353972HCID 67353972, compoundYield 46.5%

Reagents, catalysts & solvents 3

HCID 517166Dichlorocobalt hexahydrateCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Treat a 0° C. mixture of 3-cyano-2-(4,4-difluoro-piperidin-1-yl)-propionic acid methyl ester (3.74 g, 16.1 mmol) and cobalt (II) chloride hexahydrate (1.92 g, 8.07 mmol) in THF (50 mL) and water (25 mL) portion-wise with sodium borohydride (3.05 g, 80.6 mmol) and warm to room temperature and stir for 2 days under N2. Treat the reaction with 28% ammonium hydroxide (2 mL) and filter through hyflo. Remove the solvent from the filtrate in vacuo and dilute the residue with minimal water and brine and extract three times with 3:1 chloroform:isopropanol. Dry the organic layer with Na2SO4 and remove the solvent in vacuo to afford crude product. Purify on silica with a 0 to 10% methanol in CH2Cl2 gradient to afford 1.53 g (46%) of the titled product. Rf=0.43 (9/1 CH2Cl2/methanol, I2 stain). ES MS (m/z): 205 (M+).

Workup

  1. additionTreat a 0° C.
  2. additionTreat
  3. filtrationfilter through hyflo
  4. customRemove the solvent from the filtrate in vacuo
  5. additiondilute the residue with minimal water and brine
  6. extractionextract three times with 3:1 chloroform
  7. dry with materialDry the organic layer with Na2SO4
  8. customremove the solvent in vacuo
  9. customto afford crude product
  10. customPurify on silica with a 0 to 10% methanol in CH2Cl2 gradient

Sources & evidence

ORD record
ord-a7cc11c37e904bd1872d985372a9ca63
Source dataset
uspto-grants-2011_08
Patent number
US07994176B2

Reaction notes

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