Diisopropylamine → Norvaline, 2-propyl-, ethyl ester

HRID 612392Notes

Reaction equation

HRID 612392 reaction equation
[CH:1](NC(C)C)([CH3:3])[CH3:2].C([Li])CCC.[CH2:13]([O:15][C:16](=[O:29])[CH:17]([N:21]=CC1C=CC=CC=1)[CH2:18][CH2:19][CH3:20])[CH3:14].ICCC>O1CCCC1.CCCCCC>[CH2:13]([O:15][C:16](=[O:29])[C:17]([NH2:21])([CH2:18][CH2:19][CH3:20])[CH2:2][CH2:1][CH3:3])[CH3:14]

Participants

7

Reactant 4

HCID 7912DiisopropylamineHCID 336431-IodopropaneHCID 107048012-(Benzylideneamino)pentanoic acid ethyl esterHCID 178418339Butyllithium

Product 1

HCID 575027Norvaline, 2-propyl-, ethyl esterYield 67%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

A solution of 10.4 ml of diisopropylamine in 200 ml of tetrahydrofuran was combined dropwise at 0° C. with stirring under a stream of dry nitrogen with 49 ml of a 1.6 molar solution of n-butyllithium in n-hexane. After cooling to -78° C., a solution of 18.31 g of the product from stage 2 in 80 ml of tetrahydrofuran was added dropwise. The entire reaction batch was stirred for 30 minutes and a solution of 8.8 ml of 1-iodopropane in 40 ml of tetrahydrofuran was then added dropwise. The reaction batch was stirred for 16 hours, wherein the temperature slowly rose to 20° C. The solvent was removed by distillation. The resultant orange-coloured residue was redissolved in 500 ml of 1 N hydrochloric acid. After 1 hour's stirring at 20° C., extraction was performed three times with 100 ml portions of diethyl ether. The phase acidified with hydrochloric acid was adjusted to a pH of between 10 and 12 with potassium hydroxide and then extracted three times with 100 ml portions of diethyl ether. The extracts were combined, washed twice with a saturated sodium chloride solution and dried over sodium sulphate. The crude product obtained after removing the solvent by distillation was purified by passage through a silica gel column with ethyl acetate. 9.84 g of 2-amino-2-propylpentanoic acid ethyl ester (67% of th.) were obtained in the form of a slightly coloured oil.

Workup

  1. customwas combined dropwise at 0° C.
  2. stirringThe reaction batch was stirred for 16 hours
  3. customslowly rose to 20° C
  4. customThe solvent was removed by distillation
  5. dissolutionThe resultant orange-coloured residue was redissolved in 500 ml of 1 N hydrochloric acid
  6. stirringAfter 1 hour's stirring at 20° C.
  7. extractionextraction
  8. extractionextracted three times with 100 ml portions of diethyl ether
  9. washwashed twice with a saturated sodium chloride solution
  10. dry with materialdried over sodium sulphate
  11. customThe crude product obtained
  12. customafter removing the solvent
  13. distillationby distillation
  14. customwas purified by passage through a silica gel column with ethyl acetate

Sources & evidence

ORD record
ord-a35d28095a71412b948c90e3076b4eff
Source dataset
uspto-grants-1999_12
Patent number
US06004963

Reaction notes

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