Acetic Acid → N-(t-Butoxycarbonyl)-alpha-(4-hydroxy-2,3,5,6-tetrahydro-4-pyranyl)glycine, benzyl ester

HRID 2118843Notes

Reaction equation

HRID 2118843 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:17][C:18]([NH:20][CH2:21][C:22]([O:24][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].[O:32]1[CH2:37][CH2:36][C:35](=[O:38])[CH2:34][CH2:33]1.C(O)(=O)C>O1CCCC1.CCCCCC.O>[C:13]([O:17][C:18]([NH:20][CH:21]([C:35]1([OH:38])[CH2:36][CH2:37][O:32][CH2:33][CH2:34]1)[C:22]([O:24][CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:23])=[O:19])([CH3:16])([CH3:14])[CH3:15]

Participants

9

Reactant 5

HCID 176Acetic AcidHCID 7912DiisopropylamineHCID 121599Tetrahydro-4H-pyran-4-oneHCID 357720Benzyl N-(tert-butoxycarbonyl)glycinateHCID 178418339Butyllithium

Product 1

HCID 13754449N-(t-Butoxycarbonyl)-alpha-(4-hydroxy-2,3,5,6-tetrahydro-4-pyranyl)glycine, benzyl ester

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent4×HCID 8058HexaneSolvent

Conditions

Temperature
-72 °C

Procedure

A solution of diisopropylamine (17.5 ml, 0.127 moles) in 300 ml of dry tetrahydrofuran at -45° C. under argon was treated with 70 ml (0.117 moles) of 1.71M n-butyllithium (in hexane). After 20 minutes at -45° C., the mixture was cooled to -72° C. and treated with 13.3 g (0.05 moles) of dried N-(t-butoxycarbonyl)glycine, benzyl ester in 60 ml of dry tetrahydrofuran. After 50 minutes, the dark yellow homogeneous solution was treated with 5 ml (5.43 g, 0.0543 moles) of tetrahydro-4-pyranone in 50 ml of tetrahydrofuran and the temperature allowed to rise to 0° C. over 1.5 hours. A solution of 7.2 g (0.12 moles) of glacial acetic acid in 20 ml of tetrahydrofuran was added to the purple solution, and the resulting light yellow turbid mixture was poured into 1L of water and extracted with ethyl acetate. The organic layer was washed with 2% potassium bisulfate, 5% sodium bicarbonate and brine, dried (sodium sulfate) and evaporated to an oil. Chromatography on 800 ml of LPS-1 in hexane:ethyl acetate (1:1) and combination of the product fractions (Rf=0.32 in the same solvent) gave an oil which solidified on trituration with hexane yielding a total of 10.34 g of product as a white solid, melting point 90°-93° C.

Workup

  1. waitAfter 50 minutes
  2. waitto rise to 0° C. over 1.5 hours
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with 2% potassium bisulfate, 5% sodium bicarbonate and brine
  5. dry with materialdried (sodium sulfate)
  6. customevaporated to an oil
  7. customChromatography on 800 ml of LPS-1 in hexane:ethyl acetate (1:1) and combination of the product fractions (Rf=0.32 in the same solvent) gave an oil which

Sources & evidence

ORD record
ord-0162138d7bbe4596a2f6ade276ad4fe0
Source dataset
uspto-grants-1987_07
Patent number
US04680388

Reaction notes

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