Ammonium Chloride → (3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl ester

HRID 1670627Notes

Reaction equation

HRID 1670627 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C@H:12]2[C@@H:10]([O:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N-:15]=[N+:16]=[N-:17].[Na+].[Cl-].[NH4+].CO.O>O>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][C@@H:12]([N:15]=[N+:16]=[N-:17])[C@H:10]([OH:11])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 33557Sodium AzideHCID 22242641Methanol--water (1/1)HCID 87361036Racemic trans-7-oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester

Product 1

HCID 58745530(3R*,4R*)-4-azido-3-hydroxy-piperidine-1-carboxylic acid tert-butyl esterYield 42%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Heat a mixture of racemic trans-7-oxa-3-aza-bicyclo[4.1.0]heptane-3-carboxylic acid tert-butyl ester (0.56 mol, 112 g), sodium azide (1.12 mol, 73.08 g), ammonium chloride (0.56 mol, 30.07 g) and methanol/water (3:1) (1 L) at 65° C. for 16 h. Dilute the reaction mixture with water, extract with dichloromethane, and wash the organic layer with saturated sodium bicarbonate and brine solution. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate. Purify the residue on a silica gel column using 6% ethyl acetate in hexanes as eluent to obtain the title compound (42.3 g, 42%) as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ 1.48 (s, 9H), 1.84 (br s 1H), 1.97-2.01 (m, 1H), 2.74-2.82 (m, 1H), 2.88 (br s, 1H), 3.37-3.40 (m, 1H), 3.50 (br s, 1H), 3.91 (br s, 1H), 4.09 (dd, 1H). ES-MS m/z 143 [M−Boc]+.

Workup

  1. temperatureHeat
  2. extractionextract with dichloromethane
  3. washwash the organic layer with saturated sodium bicarbonate and brine solution
  4. dry with materialDry the organic layer over anhydrous sodium sulfate
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify the residue on a silica gel column

Sources & evidence

ORD record
ord-5478fcef4a3c417bb59aa048a7c53c7c
Source dataset
uspto-grants-2011_08
Patent number
US07994164B2

Reaction notes

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