L-Serine → Ethyl 2-cyanomethyl-2-phenylmethylpropanoate

HRID 1955689Notes

Reaction equation

HRID 1955689 reaction equation
[C:1]1([CH2:7][CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:16][C:17]#[N:18].C([N-]C(C)C)(C)C.[Li+].CN(P(N(C)C)(N(C)C)=O)C.N[C@H](C(O)=O)CO>C1COCC1>[C:1]1([CH2:7][CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:17]([CH2:16][C:8]([CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])#[N:18]

Participants

8

Reactant 5

HCID 5951L-SerineHCID 11534BromoacetonitrileHCID 12679HexamethylphosphoramideHCID 562367Ethyl 2-methyl-3-phenylpropanoateHCID 2724682Lithium diisopropylamide

Product 2

HCID 562367Ethyl 2-methyl-3-phenylpropanoateHCID 10704694Ethyl 2-cyanomethyl-2-phenylmethylpropanoateYield 135.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The reaction of ethyl 2-phenylmethylpropanoate (9.60 g, 50 mmol) with bromoacetonitrile (9.0 g, 75 mmol) in the presence of lithium diisopropylamide (prepared by treating diisopropylamine (6.06 g, 60 mmol) with butyllithium in hexanes (2.5M, 24 mL, 60 mmol)) in THF (150 mL) and HMPA (4.3 mL, 25 mmol), as described above in the preparation of Example 4, gave 11.95 g of the crude product as a pale yellow colored liquid. Ethyl 2-phenylmethylpropanoate was prepared as in Spencer R W, Tam T F, Thomas E, Robinson V J, Krantz A (1986) "Ynenol lactones: Synthesis and investigation of reactions relevant to their inactivation of serine proteases" J. Am. Chem. Soc., 108, 5589-5597. Flash chromatography over silica gel (hexanes-CH2Cl2, 3:2) afforded 7.86 g (68%) of the nitrile as a colorless viscous liquid. Analytical sample was prepared by bulb-to-bulb distillation (pot temp. 110°-115° C. (0.9 mmHg)).

Workup

  1. customas described above in the preparation of Example 4
  2. customgave 11.95 g of the crude product as a pale yellow colored liquid

Sources & evidence

ORD record
ord-36707f9b22384f84bfcb2a676a00cf22
Source dataset
uspto-grants-1998_07
Patent number
US05776959

Reaction notes

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