Methanol → tert-butyl N-[(2S)-4-methyl-1-oxopentan-2-yl]carbamate

HRID 64606Notes

Reaction equation

HRID 64606 reaction equation
C[O:2][C:3](=O)[C@H:4]([CH2:13][CH:14]([CH3:16])[CH3:15])[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[H-].C([Al+]CC(C)C)C(C)C.CO.[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1.O>[C:6]([NH:5][C@H:4]([CH:3]=[O:2])[CH2:13][CH:14]([CH3:15])[CH3:16])([O:8][C:9]([CH3:10])([CH3:12])[CH3:11])=[O:7]

Participants

7

Reactant 4

HCID 887MethanolHCID 9357Potassium Sodium TartrateHCID 10879384N-(tert-Butoxycarbonyl)-L-leucine methyl esterHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 104275tert-butyl N-[(2S)-4-methyl-1-oxopentan-2-yl]carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

Boc--L--Leucine methyl ester (22.7 g, 90 mmoles) in dry toluene (250 ml) under N2 was cooled to -78° and 25% di-isobutylaluminium hydride in toluene (130 ml, 225 mmoles) were added over 25 mins. keeping the temperature under -70°. The mixture was stirred for 15 mins. at -78° after completion of the addition, then MeOH (10 ml) was added cautiously. When effervescence ceased the mixture was poured into an ice-cold solution of Rochelle salt (100 ml of saturated solution+600 ml H2O). This mixture was shaken until an extractable solution was obtained. The toluene was separated and the aqueous phase re-extracted with ether (2×300 ml). Toluene and ether extracts were combined and dried (Na2SO4). The resulting oil was passed rapidly through a pad of silica gel in 15% EtOAc/petrol 40°-60°. The crude aldehyde was obtained as an oil, weight 18.68 g. Nmr showed aldehyde content to be 85%, therefore yield of aldehyde: 15.9 g (83%).

Workup

  1. customunder -70°
  2. additionat -78° after completion of the addition
  3. stirringThis mixture was shaken until an extractable solution
  4. customwas obtained
  5. customThe toluene was separated
  6. extractionthe aqueous phase re-extracted with ether (2×300 ml)
  7. dry with materialdried (Na2SO4)
  8. customwas passed rapidly through a pad of silica gel in 15% EtOAc/petrol 40°-60°

Sources & evidence

ORD record
ord-b8bd184b02c14345b883c3beaf7d2a95
Source dataset
uspto-grants-1986_09
Patent number
US04609643

Reaction notes

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