Methanol → (2S)-1-(1,2-Dioxo-3,3-dimethylpentyl)2-(1-[3-(3-pyridyl)-1-propyl]-1H-tetrazol-5-yl)azetidine

HRID 1264484Notes

Reaction equation

HRID 1264484 reaction equation
[O:1]=[C:2]([N:7]1[CH2:10][CH2:9][C@H:8]1[C:11]1[N:15]([CH2:16][CH2:17][CH2:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)[N:14]=[N:13][N:12]=1)[C:3](=[O:6])OC.[CH3:25][C:26]([Mg]Cl)([CH3:29])[CH2:27][CH3:28].[Cl-].[NH4+].CO>O1CCCC1.ClCCl>[O:1]=[C:2]([N:7]1[CH2:10][CH2:9][C@H:8]1[C:11]1[N:15]([CH2:16][CH2:17][CH2:18][C:19]2[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=2)[N:14]=[N:13][N:12]=1)[C:3](=[O:6])[C:26]([CH3:29])([CH3:25])[CH2:27][CH3:28]

Participants

7

Reactant 4

HCID 887MethanolHCID 25517Ammonium ChlorideHCID 59049300(2S)-1-(1,2-Dioxo-2-methoxyethyl)-2-(1-[3-(3-pyridyl)-1-propyl]-1H-tetrazol-5-yl)azetidineHCID 178446075HCID 178446075, compound

Product 1

HCID 9951275(2S)-1-(1,2-Dioxo-3,3-dimethylpentyl)2-(1-[3-(3-pyridyl)-1-propyl]-1H-tetrazol-5-yl)azetidineYield 8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

(2S)-1-(1,2-Dioxo-2-methoxyethyl)-2-(1-[3-(3-pyridyl)-1-propyl]-1H-tetrazol-5-yl)azetidine from Reference Example 19 (95.8 mg, 0.290 mmol, 1.0 eq) was dissolved in dry tetrahydrofuran (THF) (1.0 mL) and cooled to about −78° C. under an argon atmosphere. To this solution, 1,1-dimethylpropylmagnesium chloride in THF (380 μL of 1M, 0.380 mmol, 1.3 eq) was introduced via syringe. After stirring the resulting homogeneous mixture at about −78° C. for about 3 hours, the mixture was poured into saturated ammonium chloride and extracted into ethyl acetate. The organic phase was washed with water, dried over sodium sulfate and concentrated. Flash chromatography of the residue (0-10% methanol in dichloromethane) afforded 8.7 mg (8% yield) of the product as a colorless semisolid along with 30.3 mg recovered starting material (32% yield). 1H NMR (CDCl3) δ 0.78 (t, 3H, J=6.9); 0.97-1.18 (series of s, 6H); 1.54 and 3.17 (series of m, 8H); 3.82-4.66 (series of m, 4H); 5.33-5.90 (series of dd, 1H); 7.21-7.31 (m, 1H); 7.57 (d, 1H, J=7.7); 8.49 (s, 2H).

Workup

  1. extractionextracted into ethyl acetate
  2. washThe organic phase was washed with water
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-f74e8d761c2e4b64b4c7b8a4392fb2c9
Source dataset
uspto-grants-2003_04
Patent number
US06544976B1

Reaction notes

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