Tetrahydrofurfuryl alcohol → benzyl (3R,4R)-4-amino-3-methoxypiperidine-1-carboxylate

HRID 1676599Notes

Reaction equation

HRID 1676599 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C@@H:14]([N:17]=[N+]=[N-])[C@H:13]([O:20][CH3:21])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[NH4+].O1CCCC1CO>[Zn]>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C@@H:14]([NH2:17])[C@H:13]([O:20][CH3:21])[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7360Tetrahydrofurfuryl alcoholHCID 25517Ammonium ChlorideHCID 90891592(Rac)-(3r,4r)-4-azido-3-methoxy-piperidine-1-carboxylic acid benzyl ester

Product 1

HCID 67354303benzyl (3R,4R)-4-amino-3-methoxypiperidine-1-carboxylateYield 62.2%

Reagents, catalysts & solvents 1

HCID 23994ZincCatalyst

Procedure

A mixture of 0.123 g (0.42 mmole) of (rac)-(3R,4R)-4-azido-3-methoxy-piperidine-1-carboxylic acid benzyl ester, 0.105 g (0.39 mg-atom) of zinc, 0.20 g of ammonium chloride and 4 mL of tetrahydrofuran-methanol (1:1) was stirred at room temperature for 2 hours and then filtered through a Celite pad, washing with 25 mL of water and 25 mL of tetrahydrofuran. The combined filtrates were made strongly acidic with hydrochloric acid and extracted twice with 25 mL of ethyl acetate. The aqueous layer was made basic with potassium carbonate and extracted three times with 25 mL of ethyl acetate. The combined organic extracts were dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give 0.069 g of (rac)-(3R,4R)-4-amino-3-methoxy-piperidine-1-carboxylic acid benzyl ester as a colorless oil.

Workup

  1. filtrationfiltered through a Celite pad
  2. washwashing with 25 mL of water and 25 mL of tetrahydrofuran
  3. extractionextracted twice with 25 mL of ethyl acetate
  4. extractionextracted three times with 25 mL of ethyl acetate
  5. dry with materialThe combined organic extracts were dried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-630e5aa4c1d94cf4b412fd09d6423f98
Source dataset
uspto-grants-2011_08
Patent number
US08003785B2

Reaction notes

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