Boc-L-isoleucine methyl ester → 1,1-Dimethylethyl N-((1S,2S)-1-formyl-2-methylbutyl)carbamate

HRID 979658Notes

Reaction equation

HRID 979658 reaction equation
C[O:2][C:3](=O)[C@H:4]([C@H:13]([CH2:15][CH3:16])[CH3:14])[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>C1(C)C=CC=CC=1.CCCCCC>[C:9]([O:8][C:6]([NH:5][C@H:4]([CH:3]=[O:2])[C@H:13]([CH2:15][CH3:16])[CH3:14])=[O:7])([CH3:10])([CH3:12])[CH3:11]

Participants

5

Reactant 2

HCID 11791441Boc-L-isoleucine methyl esterHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 113902721,1-Dimethylethyl N-((1S,2S)-1-formyl-2-methylbutyl)carbamateYield 98%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A mixture of L-isoleucine methyl ester (24.3 g., 0.134 mmoles) and triethylamine (13.5 g., 0.134 mmoles) in methylene chloride (210 ml.) was prepared and a solution of ditertbutyldicarbonate (Aldrich, 29.1 g., 0.134 mmoles) in methylene chloride (25 ml.) was added dropwise to this mixture at 0° C. After completion of this addition, the mixture was allowed to warm to room temperature overnight and was then filtered. The filtrate was washed successively with water (1×100 ml.) and a saturated sodium bicarbonate solution (1×75 ml.), dried over magnesium sulfate and evaporated to yield N-(t-butoxycarbonyl)-L-isoleucine methyl ester as an oil [30.7 g.; 93% yield; 1H-NMR (CDCl3): delta 0.92 (d, J=7,6H), 1.43 (s, 9H), 3.70 (s, 3H), 4.17 (dd, J=5, 9, 1H), 5.03 (d, J=9, 1H)]. A solution of the N-(t-butoxycarbonyl)-L-isoleucine methyl ester oil (15.0 g., 61.1 mmoles) in dry toluene (260 ml.) was cooled to -78° C., and a 1M solution of diisobutyl aluminum hydride in hexane (153 ml.) was added dropwise thereto at such a rate that the temperature of the exothermic reaction did not exceed -65° C. Following 15 minutes of addition stirring at -78° C. after completion of this addition, the mixture was carefully quenched with 15 ml. of methanol (the mixture temperature was not allowed to exceed -65° C.) followed by 200 ml. of Rochelle salt solution. After warming to room temperature, the organic layer was separated and extracted with ether (3×200 ml.); additional Rochelle salt solution was added when necessary to dissolve the aluminum salts. The combined organic extract was dried over sodium sulfate and evaporated to afford a crude product as an oil. The oil was stored at -78° C. to avoid possible racemization and was used without purification in the next step [132 g., 98% yield, Rf=0.32 in 35% ether in hexane; 1H-NMR (CDCl3): delta 1.00 (d, J=7,6H), 1.46 (s, 9H), 9.65 (s, 1H)].

Workup

  1. customat such a rate that the temperature of the exothermic reaction
  2. customdid not exceed -65° C
  3. additionFollowing 15 minutes of addition
  4. additionafter completion of this addition
  5. customthe mixture was carefully quenched with 15 ml
  6. customto exceed -65° C.
  7. temperatureAfter warming to room temperature
  8. customthe organic layer was separated
  9. extractionextracted with ether (3×200 ml.)
  10. additionadditional Rochelle salt solution was added when necessary
  11. dissolutionto dissolve the aluminum salts
  12. extractionThe combined organic extract
  13. dry with materialwas dried over sodium sulfate
  14. customevaporated

Sources & evidence

ORD record
ord-c3b0229b85c64cf8b7ca1165c017848c
Source dataset
uspto-grants-1987_05
Patent number
US04668769

Reaction notes

Loading…