2-Amino-5-methylthiazole → HCID 57504746, compound

HRID 1098286Notes

Reaction equation

HRID 1098286 reaction equation
C[Al](C)C.[CH3:5][C:6]1[S:10][C:9]([NH2:11])=[N:8][CH:7]=1.[Si:12]([O:19][CH:20]1[CH2:23][N:22]([CH2:24][C@H:25]([OH:30])[C:26](OC)=[O:27])[CH2:21]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]>C(Cl)Cl>[Si:12]([O:19][CH:20]1[CH2:23][N:22]([CH2:24][C@H:25]([OH:30])[C:26]([NH:11][C:9]2[S:10][C:6]([CH3:5])=[CH:7][N:8]=2)=[O:27])[CH2:21]1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

Participants

5

Reactant 3

HCID 3517702-Amino-5-methylthiazoleHCID 16682925TrimethylaluminumHCID 57504648(S)-methyl 3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxypropanoate

Product 1

HCID 57504746HCID 57504746, compoundYield 23.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

Trimethylaluminium (1M in heptane) (3.97 mL, 3.97 mmol) was added to 5-methylthiazol-2-amine (0.434 g, 3.80 mmol) in DCM (40 mL) cooled to 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes. (S)-Methyl 3-(3-(tert-butyldimethylsilyloxy)azetidin-1-yl)-2-hydroxypropanoate (Intermediate AD3) (1 g, 3.45 mmol) in DCM (10 mL) was added and the reaction was allowed to warm to room temperature and then heated at reflux for 2 hours, then left to cool to room temperature overnight. Rochelle solution (20%; 50 mL) was added and the resulting mixture was stirred vigorously for 90 mins. The mixture was diluted with DCM (50 mL) and the layers separated. The organics were dried (MgSO4) and evaporated (733 mg). The residue was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in EtOAc to afford the product (0.300 g, 23.37%).

Workup

  1. temperatureto warm to room temperature
  2. temperatureheated
  3. temperatureat reflux for 2 hours
  4. waitleft
  5. temperatureto cool to room temperature overnight
  6. additionRochelle solution (20%; 50 mL) was added
  7. stirringthe resulting mixture was stirred vigorously for 90 mins
  8. customthe layers separated
  9. dry with materialThe organics were dried (MgSO4)
  10. customevaporated (733 mg)
  11. customThe residue was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in EtOAc

Sources & evidence

ORD record
ord-b6604c09d9cb4cc8b719909d25987aa1
Source dataset
uspto-grants-2012_03
Patent number
US08143263B2

Reaction notes

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