Sodium Hydroxide → HCID 70237825, compound

HRID 1384845Notes

Reaction equation

HRID 1384845 reaction equation
[OH-].[Na+].[CH:3]1([CH:12]([CH2:16][C:17](=[O:28])[N:18]2[CH2:27][CH2:26][C:21]3([CH2:25][CH2:24][CH2:23][CH2:22]3)[CH2:20][CH2:19]2)[C:13]([O-:15])=[O:14])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1>O.O1CCCC1.CO>[CH:3]1([CH:12]([CH2:16][C:17](=[O:28])[N:18]2[CH2:19][CH2:20][C:21]3([CH2:22][CH2:23][CH2:24][CH2:25]3)[CH2:26][CH2:27]2)[C:13]([OH:15])=[O:14])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4]1

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 86757149HCID 86757149, compound

Product 1

HCID 70237825HCID 70237825, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 6.8 g (0.17 mol) of sodium hydroxide in 60 ml of water is added to a solution of 20 g (0.0522 mol) of ethyl [R-(R*,S*)]-α-(2,3-dihydro-1H-inden-1-yl)-γ-oxo-8-azaspiro[4.5]decane-8-butanoate in a mixture of 150 ml of tetrahydrofuran and 150 ml of methanol, and the mixture is stirred for 3 h at 60° C. The mixture is concentrated, 200 ml of water are added, the solution obtained is washed with twice 150 ml of diethyl ether and then acidified at 0° C. with 6 M hydrochloric acid to pH 2 and it is extracted with twice 250 ml of dichloromethane; the organic phases are washed with brine, dried with sodium sulphate and evaporated to dryness. 16 g of [R-(R*,S*)]-α-(2,3-dihydro-1H-inden-1-yl)-γ-oxo-8-azaspiro[4.5]decane-8-butanoic acid are obtained in the form of a colourless oil; the (R*,S*) diastereoisomeric ratio=6/4. Yield 86%; 14 g (0.0295 mol) of this acid are dissolved in 320 ml of ethyl acetate, the solution is cooled to 0° C. and then a solution of 3.57 g (0.0295 mol) of (R) (+)-α-methylbenzylamine in 25 ml of ethyl acetate is added; the mixture is stirred at room temperature for 16 h, the precipitate formed is filtered, it is stirred in 30 ml of ethyl acetate, it is filtered and then it is dried; 7 g of a white solid of melting point 155-156° C. are obtained; 75 ml of water are added to a suspension of 7 g of the preceding solid, the solution is cooled to 0° C. and acidified with 6 M hydrochloric acid to pH 2; the mixture is stirred for 15 min with 170 ml of diisopropyl ether, the organic phase is decanted off and the aqueous phase is extracted with 170 ml of diisopropyl ether; the organic phases are washed with brine, dried over sodium sulphate and then evaporated to dryness. 4.9 g of [R-(R*,S*)]-α-(2,3-dihydro-1H-inden-1-yl)-γ-oxo-8-azaspiro[4.5]decane-8-butanoic acid are obtained in the form of a white solid; (R*,S*) diastereomeric ratio >99%. The product melts at 137° C. with decomposition. [α]D=−26° (c=5%, ethanol)

Workup

  1. concentrationThe mixture is concentrated
  2. addition200 ml of water are added
  3. customthe solution obtained
  4. washis washed with twice 150 ml of diethyl ether
  5. customacidified at 0° C. with 6 M hydrochloric acid to pH 2 and it
  6. extractionis extracted with twice 250 ml of dichloromethane
  7. washthe organic phases are washed with brine
  8. dry with materialdried with sodium sulphate
  9. customevaporated to dryness

Sources & evidence

ORD record
ord-5fd1d76600fc4fbd9b4666f9443f62b5
Source dataset
uspto-grants-2001_07
Patent number
US06262060B1

Reaction notes

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