Diisopropylethylamine → 1,1-Dimethylethyl N-((6-chloro-4-hydroxy-2-oxo-2',3',5',6'-tetrahydro-spiro[naphthalene-1,4'-pyran]-3-yl)carbonyl)-L-alaninate

HRID 2078173Notes

Reaction equation

HRID 2078173 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[C:8]1([CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)[C:7](=[O:17])[C:6]([C:18](OCC)=[O:19])=[C:5]2[OH:23].C(N(C(C)C)C(C)C)C.Cl.[C:34]([O:38][C:39](=[O:43])[C@H:40]([CH3:42])[NH2:41])([CH3:37])([CH3:36])[CH3:35]>O1CCOCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:14](=[CH:15][CH:16]=1)[C:8]1([CH2:13][CH2:12][O:11][CH2:10][CH2:9]1)[C:7](=[O:17])[C:6]([C:18]([NH:41][C@H:40]([C:39]([O:38][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:43])[CH3:42])=[O:19])=[C:5]2[OH:23]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 11275390tert-Butyl alaninate hydrochlorideHCID 67099777HCID 67099777, compound

Product 1

HCID 670992391,1-Dimethylethyl N-((6-chloro-4-hydroxy-2-oxo-2',3',5',6'-tetrahydro-spiro[naphthalene-1,4'-pyran]-3-yl)carbonyl)-L-alaninateYield 66.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Ethyl 6-chloro-4-hydroxy-2-oxo-2′,3′,5′,6′-tetrahydro-spiro[naphthalene-1,4′-pyran]-3-carboxylate (610 mg, 1811 μmol, prepared in Example 1 A-C) was dissolved in 1,4-dioxane (1811 μL) and N-ethyl-N-isopropylpropan-2-amine (947 μL, 5434 μmol). L-Alanine t-butyl ester hydrochloride (494 mg, 2717 μmol) was added, and the reaction mixture was heated to 80° C. for 24 hours. The reaction mixture was then cooled to ambient temperature, diluted with 150 mL of EtOAc, added to a separatory funnel, partitioned with NaHCO3 (saturated, aqueous), washed 2 times with 50 mL of NaHCO3 (saturated, aqueous), separated, dried over Na2SO4, and concentrated in vacuo to give the title compound (525 mg) as an oil after flash chromatography. MS (m/z)=436 (M+H)+.

Workup

  1. temperatureThe reaction mixture was then cooled to ambient temperature
  2. additionadded to a separatory funnel
  3. custompartitioned with NaHCO3 (saturated, aqueous)
  4. washwashed 2 times with 50 mL of NaHCO3 (saturated, aqueous)
  5. customseparated
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6a5dc341ed3d4e2e93569286d603e680
Source dataset
uspto-grants-2011_04
Patent number
US07928139B2

Reaction notes

Loading…