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

HRID 2078171Notes

Reaction equation

HRID 2078171 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.[NH2:34][C:35]([CH3:44])([CH3:43])[C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37]>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:34][C:35]([CH3:44])([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH3:43])=[O:19])=[C:5]2[OH:23]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 12186776Tert-butyl 2-amino-2-methylpropanoate hydrochlorideHCID 67099777HCID 67099777, compound

Product 1

HCID 670998271,1-Dimethylethyl N-((6-chloro-4-hydroxy-2-oxo-2',3',5',6'-tetrahydro-spiro[naphthalene-1,4'-pyran]-3-yl)carbonyl)-2-methylalaninateYield 60.8%

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 (320 mg, 950 μmol, prepared according to Example 1 A-C) was dissolved in 1,4-dioxane (950 μL) and N-ethyl-N-isopropylpropan-2-amine (507 μL, 2851 μmol) before tert-butyl 2-amino-2-methylpropanoate hydrochloride (279 mg, 1425 μmol) was added. The resulting mixture was heated at 80° C. for 24 hours and then diluted with 150 mL of EtOAc. The resulting mixture was added to a separatory funnel, partitioned with NaHCO3 (saturated, aqueous), washed with saturated aqueous NaHCO3 (2×75 mL), separated, dried over Na2SO4, and concentrated in vacuo to give the title compound (260 mg) after chromatography as an amorphous solid. MS (m/z)=394 (M+H-tert-butyl)+.

Workup

  1. additionThe resulting mixture was added to a separatory funnel
  2. custompartitioned with NaHCO3 (saturated, aqueous)
  3. washwashed with saturated aqueous NaHCO3 (2×75 mL)
  4. customseparated
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f15e20a2b54047f4a78ca9fa44f2c12e
Source dataset
uspto-grants-2011_04
Patent number
US07928139B2

Reaction notes

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