Hydrochloric Acid → 2-(3-Tert. butylamino-2-hydroxypropoxy)-3-cyanopyridine hydrochloride

HRID 972733Notes

Reaction equation

HRID 972733 reaction equation
C1(C2[N:11]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH2:10][CH:9]([CH2:16][O:17][C:18]3[C:23]([C:24]#[N:25])=[CH:22][CH:21]=[CH:20][N:19]=3)[O:8]2)C=CC=CC=1.[ClH:26]>C(OCC)C>[ClH:26].[C:12]([NH:11][CH2:10][CH:9]([OH:8])[CH2:16][O:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][CH:21]=[CH:20][N:19]=1)([CH3:15])([CH3:13])[CH3:14]

Participants

4

Reactant 2

HCID 313Hydrochloric Acid2×HCID 20288718HCID 20288718, compound

Product 1

HCID 100853592-(3-Tert. butylamino-2-hydroxypropoxy)-3-cyanopyridine hydrochloride

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To S -2-phenyl-3-tert. butyl-5-hydroxymethyloxazolidine (7 grams, 0.03 moles) in 35 ml. of N,N-dimethylformamide (DMF) is added 1.3 grams (0.03 moles of sodium hydride (57% dispersion in mineral oil). This mixture is heated 5 minutes over steam and then is allowed to stir 15 minutes at room temperature. 4.1 grams (0.03 moles) of 2-chloro-3-cyanopyridine in 20 ml of DMF is then added and the resultant reaction mixture is stirred four hours at room temperature. Water is then added and an oil separates. This oil is extracted three times with 25 ml of chloroform each time. This chloroform exrract is dried over sodium sulfate and concentrated under reduced pressure (20 mm) over steam to yield the product, S -2-phenyl-3-tert. butyl-5-(3-cyano-2-pyridyloxymethyl)oxazolidine, as an oil. This oil is then suspended in 1N HCl (50 ml), heated 5 minutes over steam and then is stirred for 15 minutes at room temperature. The solution obtained is then extracted twice with 25 ml of diethylether each time. The extracted aqueous layer is made basic by addition of saturated aqueous sodium carbonate solution. This aqueous solution is then extracted with ethyl acetate (3 × 25 ml) and the ethylacetate solution is dried over sodium sulfate. The dried ethyl acetate solution is then concentrated under reduced pressure (20 mm) over steam to yield an oil. This oil is chromatographed on alumina. The chromatographic fractions are concentrated to yield an oil which is dissolved in diethyl ether. Ethanolic HCl (saturated solution) is added to this ether solution until solid separation is substantially complete. The separated semi-solid is recrystallized from isopropanol/ether (ether added to isopropanol to the point of turbidity) to yield 1 gram of S -2-(3-tert. butylamino-2-hydroxypropoxy)-3-cyanopyridine hydrochloride, melting at 161°-163° C.

Workup

  1. temperatureheated 5 minutes over steam
  2. customThe solution obtained
  3. extractionis then extracted twice with 25 ml of diethylether each time
  4. additionThe extracted aqueous layer is made basic by addition of saturated aqueous sodium carbonate solution
  5. extractionThis aqueous solution is then extracted with ethyl acetate (3 × 25 ml)
  6. dry with materialthe ethylacetate solution is dried over sodium sulfate
  7. concentrationThe dried ethyl acetate solution is then concentrated under reduced pressure (20 mm) over steam
  8. customto yield an oil
  9. customThis oil is chromatographed on alumina
  10. concentrationThe chromatographic fractions are concentrated
  11. customto yield an oil which
  12. customThe separated semi-solid is recrystallized from isopropanol/ether (ether
  13. additionadded to isopropanol to the point of turbidity)

Sources & evidence

ORD record
ord-b54e6ea52c8a477e91abfe6550151d88
Source dataset
uspto-grants-1977_10
Patent number
US04053605

Reaction notes

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