Sodium hydride → Ethyl 6''-chloro-4''-hydroxy-5,5-dimethyl-2''-oxo-dispiro[1,3-dioxane-2,1'-cyclohexane-4',1''-naphthalene]-3''-carboxylate

HRID 1868827Notes

Reaction equation

HRID 1868827 reaction equation
[H-].[Na+].C(=N/[OH:11])\C1C=CC=CC=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2([C:32]([O:34]CC)=O)[CH2:24][CH2:23][C:22]3([O:29][CH2:28][C:27]([CH3:31])([CH3:30])[CH2:26][O:25]3)[CH2:21][CH2:20]2)=[C:15]([C:37]#[C:38][C:39]([O:41][CH2:42][CH3:43])=[O:40])[CH:14]=1>O1CCOCC1.CN(C=O)C>[Cl:12][C:13]1[CH:14]=[C:15]2[C:16](=[CH:17][CH:18]=1)[C:19]1([CH2:20][CH2:21][C:22]3([O:29][CH2:28][C:27]([CH3:31])([CH3:30])[CH2:26][O:25]3)[CH2:23][CH2:24]1)[C:32](=[O:34])[C:38]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[C:37]2[OH:11]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 5324611Benzaldehyde OximeHCID 67099900Ethyl 4'-(4-chloro-2-(3-ethoxy-3-oxoprop-1-ynyl)phenyl)-5,5-dimethyl-spiro[1,3-dioxane-2,1'-cyclohexane]-4'-carboxylate

Product 1

HCID 67099722Ethyl 6''-chloro-4''-hydroxy-5,5-dimethyl-2''-oxo-dispiro[1,3-dioxane-2,1'-cyclohexane-4',1''-naphthalene]-3''-carboxylateYield 64.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

A stirred mixture of NaH (60% dispersion in mineral oil (0.39 mL, 9.3 mmol)) in 40 mL dioxane at room temperature, was treated with a mixture of (E)-benzaldehyde oxime (1.0 g, 8.6 mmol) in 40 mL DMF. The resulting mixture was stirred for 30 minutes. The mixture was then cooled to 0° C. and treated with a mixture of ethyl 4′-(4-chloro-2-(3-ethoxy-3-oxoprop-1-ynyl)phenyl)-5,5-dimethyl-spiro[1,3-dioxane-2,1′-cyclohexane]-4′-carboxylate (3.6 g, 7.8 mmol) in 30 mL DMF. The resulting mixture was stirred for 1 hour. The mixture was then carefully quenched with 10 mL H2O and brought to a pH of 5 by addition of 10% HCl. The mixture was extracted with ethyl ether (3×50 mL). The combined organic layers were washed with brine (20 mL), dried over anhydrous Na2SO4, concentrated in vacuo, and purified by column chromatography eluting with 20-30% EtOAc to give 2.2 g of the product as a pale yellow solid. MS (m/z)=435 (M+H)+.

Workup

  1. stirringThe resulting mixture was stirred for 1 hour
  2. customThe mixture was then carefully quenched with 10 mL H2O
  3. additionbrought to a pH of 5 by addition of 10% HCl
  4. extractionThe mixture was extracted with ethyl ether (3×50 mL)
  5. washThe combined organic layers were washed with brine (20 mL)
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. custompurified by column chromatography
  9. washeluting with 20-30% EtOAc

Sources & evidence

ORD record
ord-8672b06c86ab4b828fb3eaffc7d34677
Source dataset
uspto-grants-2009_12
Patent number
US07635715B2

Reaction notes

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