Tert-Butyl nitrite → Methyl 2-chloro-4-(methoxymethyl)-1,3-thiazole-5-carboxylate

HRID 1948303Notes

Reaction equation

HRID 1948303 reaction equation
N(OC(C)(C)C)=O.N[C:9]1[S:10][C:11]([C:17]([O:19][CH3:20])=[O:18])=[C:12]([CH2:14][O:15][CH3:16])[N:13]=1.[Cl:21]C1C=C(C(OCC)=O)NC=1C>CC#N>[CH3:20][O:19][C:17]([C:11]1[S:10][C:9]([Cl:21])=[N:13][C:12]=1[CH2:14][O:15][CH3:16])=[O:18]

Participants

5

Reactant 3

HCID 10906Tert-Butyl nitriteHCID 25220423Methyl 2-amino-4-(methoxymethyl)thiazole-5-carboxylateHCID 66707189ethyl 4-chloro-5-methyl-1H-pyrrole-2-carboxylate

Product 1

HCID 45117583Methyl 2-chloro-4-(methoxymethyl)-1,3-thiazole-5-carboxylate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

tert-Butyl nitrite (2.2 ml, 18.6 mmol) and cuprous chloride (1.5 g) were suspended in anhydrous CH3CN (100 ml). Methyl 2-amino-4-(methoxymethyl)-1,3-thiazole-5-carboxylate (2.5 g) prepared as described in (Kennedy, Alan R. et al. Acta Crystallographica, Section C: Crystal Structure Communications (1999, C55 (7) 2) was added in one portion. The mixture was stirred at room temperature for 2 h and the temperature was raised to 70° C. for 1 h. The mixture was cooled to room temperature and filtered. The filtrate was poured into 6 N HCl, extracted with EtOAc, dried with MgSO4 and concentrated to a black oil. Flash purification on silica gel with gradient elution (hexane to EtOAc) yielded product as a yellow liquid (0.82 g). NMR: 3.31 (s, 3H), 3.85 (s, 3H), 4.71 (s, 2H).

Workup

  1. temperaturethe temperature was raised to 70° C. for 1 h
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered
  4. additionThe filtrate was poured into 6 N HCl
  5. extractionextracted with EtOAc
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated to a black oil
  8. customFlash purification on silica gel
  9. washwith gradient elution (hexane to EtOAc)

Sources & evidence

ORD record
ord-cf687b9b49d141b38d96de214d5cb172
Source dataset
uspto-grants-2013_03
Patent number
US08399489B2

Reaction notes

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