Cornforth reagent → (1,1-Dimethyl-2-oxoethyl)carbamic acid benzyl ester

HRID 626911Notes

Reaction equation

HRID 626911 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]([CH3:19])([CH3:18])[C:13](OCC)=[O:14])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].C([Al+]CC(C)C)C(C)C.[Cr](O[Cr]([O-])(=O)=O)([O-])(=O)=O.[NH+]1C=CC=CC=1.[NH+]1C=CC=CC=1>C1(C)C=CC=CC=1>[CH3:19][C:12]([NH:11][C:9](=[O:10])[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([CH3:18])[CH:13]=[O:14]

Participants

5

Reactant 3

HCID 2724130Cornforth reagentHCID 21225700DiisobutylaluminumhydrideHCID 89649322Ethyl 2-{[(benzyloxy)carbonyl]amino}-2-methylpropanoate

Product 1

HCID 14578675(1,1-Dimethyl-2-oxoethyl)carbamic acid benzyl esterYield 47.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of ethyl 2-(benzyloxycarbonylamino)-2-methyl-propanoate (which may be prepared as described in Description 33) (4667 mg, 17.59 mmol) in toluene (100 mL) cooled to −78° C. was added diisobutyl aluminium hydride (1 M in toluene) (61.57 mL, 61.57 mmol) as a thin stream over approximately 2 minutes. The mixture was stirred at −78° C. over 30 minutes then allowed to warm to 0° C. and stirred over 1.5 hours. The reaction mixture was quenched by addition of a saturated solution of Rochelle's salt. The quenched mixture was stirred over 1 hour, then extracted into ether (3 times). The combined ethereal extracts were dried over magnesium sulphate, filtered and evaporated to a clear oil. The oil was dissolved in DCM (60 mL) and 4A molecular sieves (4 g) and pyridinium dichromate (16544.34 mg, 43.98 mmol) were added and the mixture stirred at room temperature overnight. The reaction mixture was filtered over kieselguhr and the filtrate evaporated to a dark brown oil. Purification by silica gel column chromatography (20% EtOAc in isohexane) yielded benzyl N-(1,1-dimethyl-2-oxo-ethyl)carbamate (D34) (1840 mg, 8.3164 mmol, 47.3% yield) as a clear oil;

Workup

  1. temperatureto warm to 0° C.
  2. stirringstirred over 1.5 hours
  3. customThe reaction mixture was quenched by addition of a saturated solution of Rochelle's salt
  4. stirringThe quenched mixture was stirred over 1 hour
  5. extractionextracted into ether (3 times)
  6. dry with materialThe combined ethereal extracts were dried over magnesium sulphate
  7. filtrationfiltered
  8. customevaporated to a clear oil
  9. dissolutionThe oil was dissolved in DCM (60 mL)
  10. stirringthe mixture stirred at room temperature overnight
  11. filtrationThe reaction mixture was filtered over kieselguhr
  12. customthe filtrate evaporated to a dark brown oil
  13. customPurification by silica gel column chromatography (20% EtOAc in isohexane)

Sources & evidence

ORD record
ord-c64cfb2831e946b187404b7cf787b285
Source dataset
uspto-grants-2016_04
Patent number
US09309254B2

Reaction notes

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