Dimethylformamide → HCID 178455306, compound

HRID 2088123Notes

Reaction equation

HRID 2088123 reaction equation
[CH2:1]([N:8]1[C@@H:13]2[C@@H:14]([C:16]#[N:17])[CH2:15][C@@:9]1([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C@H:10]([O:18][Si:19]([C:22]([CH3:25])([CH3:24])[CH3:23])([CH3:21])[CH3:20])[CH2:11][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N-:32]=[N+:33]=[N-:34].[Na+].Cl.C(N(CC)CC)C.CN(C)C=O>O>[CH2:1]([N:8]1[C@@H:13]2[C@@H:14]([C:16]3[NH:34][N:33]=[N:32][N:17]=3)[CH2:15][C@@:9]1([C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C@H:10]([O:18][Si:19]([C:22]([CH3:24])([CH3:25])[CH3:23])([CH3:21])[CH3:20])[CH2:11][CH2:12]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 11130Triethylamine hydrochlorideHCID 33557Sodium AzideHCID 69890351(1R*,2R*,5S*,6S*)-8-Benzyl-2-(tert-butyldimethylsilyloxy)-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane

Product 1

HCID 178455306HCID 178455306, compoundYield 99.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of (1R*,2R*,5S*,6S*)-8-benzyl-2-(tert-butyldimethylsilyloxy)-6-cyano-1-phenyl-8-azabicyclo[3.2.1]octane (Description 42; 43 g), sodium azide (27 g), triethylamine hydrochloride (55 g) and N,N-dimethylformamide (150 ml) was stirred at +130° C. for 7 hours. The reaction mixture was cooled to room temperature, treated with water (500 ml) and extracted into ethyl acetate (4×200 ml). The combined organic extracts were washed with water (3×200 ml) and brine. The combined water layers were extracted again with ethyl acetate (2×200 ml). The organic phase was washed with small amount of water (50 ml). The combined organic extracts were dried (Na2SO4) and concentrated to give crude (1R*,2R*,5S*,6S*)-8-benzyl-2-(tert-butyldimethylsilyloxy)-1-phenyl-6-(tetrazol-5-yl]-8-azabicyclo[3.2.1]octane (47 g), which was mixed with potassium carbonate (25 g) and acetonitrile (220 ml), warmed up to +70° C. and finally treated with 2-methoxyethoxymethyl chloride (20 ml). The reaction mixture was stirred for 15 minutes, cooled to room temperature, then treated with water (500 ml) and extracted into ethyl acetate (3×200 ml). The combined organic extracts were dried (Na2SO4) and concentrated to give a 1:1.5 mixture of isomers A and B, respectively. Regioisomers were separated by chromatography on silica gel (iso-hexane:diethyl ether).

Workup

  1. extractionextracted into ethyl acetate (4×200 ml)
  2. washThe combined organic extracts were washed with water (3×200 ml) and brine
  3. extractionThe combined water layers were extracted again with ethyl acetate (2×200 ml)
  4. washThe organic phase was washed with small amount of water (50 ml)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f6e3d0d9c13643e1bf6ffdf76c5ab737
Source dataset
uspto-grants-2004_04
Patent number
US06727249B2

Reaction notes

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