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

HRID 980581Notes

Reaction equation

HRID 980581 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 1.71 M 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 1 L 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-1886a04539c04a7aacafcd881d92dc33
Source dataset
uspto-grants-1987_01
Patent number
US04638060

Reaction notes

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