Hydrochloric Acid → tert-Butyl (R)-6-Cyano-5-hydroxy-3-oxohexanoate

HRID 610634Notes

Reaction equation

HRID 610634 reaction equation
C([N-]C(C)C)(C)C.[Li+].[C:9]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])(=[O:11])[CH3:10].[C:17]([CH2:19][C@@H:20]([OH:27])[CH2:21][C:22](OCC)=[O:23])#[N:18].Cl>O1CCCC1>[C:17]([CH2:19][C@@H:20]([OH:27])[CH2:21][C:22](=[O:23])[CH2:10][C:9]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])#[N:18]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 10908tert-Butyl acetateHCID 2724682Lithium diisopropylamideHCID 2733879Ethyl (3R)-4-cyano-3-hydroxybutanoate

Product 1

HCID 9794547tert-Butyl (R)-6-Cyano-5-hydroxy-3-oxohexanoate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred -50° C. solution of lithium diisopropylamide (100 kg of 2 M) in tetrahydrofuranheptane was added tertiary-butyl acetate (30 kg, 255 mol) followed by a rinse of 3 kg of tetrahydrofuran, and the mixture was stirred to -45° C. to -5° C. for 50 minutes. (R)-4-cyano-3-hydroxybutyric acid, ethyl ester (Step A) (10 kg, 64 mol) as a solution in 30 kg of tetrahydrofuran was then added to the previous mixture. The reaction mixture was stirred for 30 minutes at -5° C. to -30° C., and transferred to 240 L of 0° C. 2.8N aqueous hydrochloric acid solution. The aqueous layer was extracted with 50 kg of ethyl acetate, the aqueous layer was separated and reextracted with 36 kg of ethyl acetate, the extracts are combined, and concentrated in vacuo to afford crude (5R)-1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxo-hexanoate which was not isolated. A small sample was purified by column chromatography on flash silica gel eluting with 1:1 hexane:ethyl acetate.

Workup

  1. washa rinse of 3 kg of tetrahydrofuran
  2. stirringThe reaction mixture was stirred for 30 minutes at -5° C. to -30° C.
  3. customtransferred to 240 L of 0° C
  4. extractionThe aqueous layer was extracted with 50 kg of ethyl acetate
  5. customthe aqueous layer was separated
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0cf543548d3c4482a367a470631b5e20
Source dataset
uspto-grants-1999_12
Patent number
US05998633

Reaction notes

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