tert-Butyl acetate → TERT-BUTYL (S)-4-(CBZ-AMINO)-5-METHYL-3-OXOHEXANOATE

HRID 1599692Notes

Reaction equation

HRID 1599692 reaction equation
[CH3:1][CH:2]([C@H:4]([NH:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[C:5]([OH:7])=O)[CH3:3].[C:19]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])(=[O:21])[CH3:20].[Li+].CC([N-]C(C)C)C.[N-]1C=CN=C1>O1CCCC1>[C:23]([O:22][C:19](=[O:21])[CH2:20][C:5](=[O:7])[C@@H:4]([NH:8][C:9]([O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:10])[CH:2]([CH3:1])[CH3:3])([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 10908tert-Butyl acetateHCID 726987N-Carbobenzoxy-L-valineHCID 2724682Lithium diisopropylamideHCID 3386966Imidazolate

Product 1

HCID 11221808TERT-BUTYL (S)-4-(CBZ-AMINO)-5-METHYL-3-OXOHEXANOATEYield 98.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To an ice-cooled solution of Z-Valine (5 g, 19.9 mmol) in 60 ml tetrahydrofuran was added N,N'-carbonyldiimidazole (3.55 g, 22.3 mmol) in one portion and the resulting mixture stirred for 3 h. t-Butyl acetate (13.5 ml, 100 mmol) was added dropwise to a solution of LDA (90 mmol in tetrahydrofuran (270 ml) at -78° C. After 30 min, the imidazolide solution was added dropwise via double-ended needle to the enolate. The resulting mixture was stirred for 2 h until the temperature rose to -15° C. The reaction was quenched with 400 ml saturated aqueous NH4Cl and extracted with ether (3×200 ml). The combined organic extracts were washed with 2N aqueous HCl (50 ml), saturated aqueous NaHCO3 (2×50 ml), dried over magnesium sulfate and evaporated to dryness in vacuo. The residue was purified by column chromatography on silica gel using ethyl acetate-hexane (1:4) as an eluent to give the product as a colorless oil (6.88 g).

Workup

  1. customrose to -15° C
  2. customThe reaction was quenched with 400 ml saturated aqueous NH4Cl
  3. extractionextracted with ether (3×200 ml)
  4. washThe combined organic extracts were washed with 2N aqueous HCl (50 ml), saturated aqueous NaHCO3 (2×50 ml)
  5. dry with materialdried over magnesium sulfate
  6. customevaporated to dryness in vacuo
  7. customThe residue was purified by column chromatography on silica gel

Sources & evidence

ORD record
ord-9720b69a21d2438a839b4253111162a2
Source dataset
uspto-grants-1998_04
Patent number
US05741892

Reaction notes

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