Methyl N-(triethylammoniosulfonyl)carbamate → 6,7-dihydro-2-(phenoxymethyl)-oxazolo[4,5-c]pyridine-5(4H)-carboxylic acid 1,1-dimethylethyl ester

HRID 1529560Notes

Reaction equation

HRID 1529560 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([NH:15][C:16](=O)[CH2:17][O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:9]1)=[O:7])([CH3:4])[CH3:3].CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1.C([O-])(O)=O.[Na+]>[CH3:4][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[O:14][C:16]([CH2:17][O:18][C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[N:15][C:10]=2[CH2:9]1)=[O:7])([CH3:1])[CH3:3]

Participants

5

Reactant 2

HCID 2724994Methyl N-(triethylammoniosulfonyl)carbamate2×HCID 666085334-Oxo-3-[(phenoxyacetyl)amino]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester

Product 1

HCID 666088866,7-dihydro-2-(phenoxymethyl)-oxazolo[4,5-c]pyridine-5(4H)-carboxylic acid 1,1-dimethylethyl esterYield 33%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
120 °C

Procedure

A suspension of 4-oxo-3-[(phenoxyacetyl)amino]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester (0.36 g, 1.0 mmol) and Burgess reagent (0.30 g, 1.25 mmol) in THF (4 mL) was stirred at 120° C. for 10 minutes under microwave irradiation. Then additional Burgess reagent (0.30 g, 1.25 mmol) was added and the mixture stirred at 150° C. for a further 5 minutes under microwave irradiation. The mixture was diluted with a saturated solution of NaHCO3 and extracted with AcOEt. The organic layer was separated, dried (Na2SO4), filtered and the solvent evaporated in vacuo. The crude product was purified by flash column chromatography (silica; AcOEt in DCM 99/1 to 80/20). The desired fractions were collected and the solvents evaporated in vacuo to yield 6,7-dihydro-2-(phenoxymethyl)-oxazolo[4,5-c]pyridine-5(4H)-carboxylic acid 1,1-dimethylethyl ester (0.11 mg, 33% yield). C18H22N2O4 LCMS: Rt 2.87, m/z 331 [M+H]+ (using method, LC-MS Method 3).

Workup

  1. stirringthe mixture stirred at 150° C. for a further 5 minutes under microwave irradiation
  2. extractionextracted with AcOEt
  3. customThe organic layer was separated
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customthe solvent evaporated in vacuo
  7. customThe crude product was purified by flash column chromatography (silica; AcOEt in DCM 99/1 to 80/20)
  8. customThe desired fractions were collected
  9. customthe solvents evaporated in vacuo

Sources & evidence

ORD record
ord-b5b44722fce848f5b5779a1f17754799
Source dataset
uspto-grants-2015_07
Patent number
US09090632B2

Reaction notes

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