Ethyl chloroformate → 2-Dimethylamino-1-[spiro(cyclopentane-1,1'-indene)-3'-yl]ethanol

HRID 1856288Notes

Reaction equation

HRID 1856288 reaction equation
Cl[C:2](OCC)=O.[OH-].[Na+].[CH3:9][NH:10][CH2:11][CH:12]([C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]2([CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:15]=1)[OH:13]>O.C(Cl)(Cl)Cl>[CH3:9][N:10]([CH3:2])[CH2:11][CH:12]([C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[C:16]2([CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:15]=1)[OH:13]

Participants

6

Reactant 3

HCID 10928Ethyl chloroformateHCID 14798Sodium HydroxideHCID 192124Kabi 2023

Product 1

HCID 233464542-Dimethylamino-1-[spiro(cyclopentane-1,1'-indene)-3'-yl]ethanol

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6212ChloroformSolvent

Conditions

Temperature
10 °C

Procedure

Ethyl chloroformate (0.7 g) and sodium hydroxide (0.3 g) dissolved in water (10 ml) are added to 2-methylamino-1-[spiro(cyclopentane-1,1'-indene)-3'-yl]-ethanol (1.3 g) in chloroform (25 ml). The mixture is stirred vigorously for 2 hours at about 10° C. The chloroform layer is separated, washed with water and dried. The solvent is removed in vacuo and the residual crude 2-(N-ethoxycarbonyl-N-methylamino)-1-[spiro(cyclopentane-1,1'-indene)-3'-yl]ethanol is dissolved in tetrahydrofuran (75 ml) and added to lithium aluminium hydride (2.0 g) in tetrahydrofuran (25 ml). The mixture is refluxed for 3 hours, and the excess of hydride is destroyed with a slight excess of saturated aqueous sodium sulphate solution. The inorganic salt precipitate is filtered off and washed with tetrahydrofuran. The combined filtrate and washings are dried over sodium sulphate and the solvent is removed under reduced pressure. The crude title compound is dissolved in acetonitrile and treated with a slight excess of oxalic acid dissolved in acetonitrile. The slowly depositing hydrogen oxalate is collected by filtration and recrystallization from acetonitrile; m.p. 133°-134° C.

Workup

  1. customThe chloroform layer is separated
  2. washwashed with water
  3. customdried
  4. customThe solvent is removed in vacuo
  5. dissolutionthe residual crude 2-(N-ethoxycarbonyl-N-methylamino)-1-[spiro(cyclopentane-1,1'-indene)-3'-yl]ethanol is dissolved in tetrahydrofuran (75 ml)
  6. additionadded to lithium aluminium hydride (2.0 g) in tetrahydrofuran (25 ml)
  7. temperatureThe mixture is refluxed for 3 hours
  8. customthe excess of hydride is destroyed with a slight excess of saturated aqueous sodium sulphate solution
  9. filtrationThe inorganic salt precipitate is filtered off
  10. washwashed with tetrahydrofuran
  11. dry with materialThe combined filtrate and washings are dried over sodium sulphate
  12. customthe solvent is removed under reduced pressure
  13. dissolutionThe crude title compound is dissolved in acetonitrile
  14. additiontreated with a slight excess of oxalic acid
  15. dissolutiondissolved in acetonitrile
  16. filtrationThe slowly depositing hydrogen oxalate is collected by filtration and recrystallization from acetonitrile

Sources & evidence

ORD record
ord-b474d96c04e644748a69e0e4948f7d1a
Source dataset
uspto-grants-1980_08
Patent number
US04218472

Reaction notes

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