Sodium borohydride → N-[(1RS)-1-hydroxymethyl-2-(5-thiazolyl)ethyl]acetamide

HRID 1280657Notes

Reaction equation

HRID 1280657 reaction equation
[BH4-].[Na+].[C:3]([NH:6][CH:7]([CH2:13][C:14]1[S:18][CH:17]=[N:16][CH:15]=1)[C:8](OCC)=[O:9])(=[O:5])[CH3:4]>C(O)C>[OH:9][CH2:8][CH:7]([NH:6][C:3](=[O:5])[CH3:4])[CH2:13][C:14]1[S:18][CH:17]=[N:16][CH:15]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydride2×HCID 86584439HCID 86584439, compound

Product 1

HCID 22747872N-[(1RS)-1-hydroxymethyl-2-(5-thiazolyl)ethyl]acetamideYield 63.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

0.4 g of sodium borohydride is added to a solution of 1.2 g of ethyl (2RS)-2-acetylamino-3-(5-thiazolyl)propanoate in 20 cm3 of ethanol, followed by stirring under an inert atmosphere at a temperature in the region of 20° C. After 18 hours, a further 0.1 g of sodium borohydride is added and the mixture is then stirred for 24 hours at a temperature in the region of 20° C. The reaction medium is concentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C. The residue is taken up in 10 cm3 of water and extracted with 3 times 30 cm3 of ethyl acetate. The organic phase is dried over magnesium sulphate, filtered and concentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C. The residue is chromatographed under an argon pressure of 60 kPa on a column of silica gel (particle size 40-63μ; diameter 3.5 cm; height 31 cm), eluting with 100 cm3 it of dichloromethane, 600 cm3 of a dichloromethane/methanol mixture (98/2 by volume), 500 cm3 of a dichloromethane/-methanol mixture (96/4 by volume) and 1 dm3 of a dichloromethane/methanol mixture (90/10 by volume). The fractions containing the expected product are combined and then concentrated under the above conditions. 0.63 g of N-[(1RS)-1-hydroxymethyl-2-(5-thiazolyl)-ethyl]acetamide is obtained in the form of a yellow oil [1H NMR spectrum (300 MHz, (CD3)2SO-d6, δ in ppm): 1.80 (s: 3H); 2.85 (dd, J=15 and 9 Hz: 1H); 3.16 (dd, J=15 and 5 Hz: 1H); from 3.25 to 3.45 (mt: 2H); 3.87 (mt: 1H); 4.85 (mt: 1H); 7.65 (s: 1H); 7.79 (d, J=8.5 Hz: 1H); 8.91 (s: 1H)].

Workup

  1. stirringthe mixture is then stirred for 24 hours at a temperature in the region of 20° C
  2. concentrationThe reaction medium is concentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C
  3. extractionextracted with 3 times 30 cm3 of ethyl acetate
  4. dry with materialThe organic phase is dried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure (1 kPa) at a temperature in the region of 40° C
  7. customThe residue is chromatographed under an argon pressure of 60 kPa on a column of silica gel (particle size 40-63μ; diameter 3.5 cm; height 31 cm)
  8. washeluting with 100 cm3 it of dichloromethane, 600 cm3 of a dichloromethane/methanol mixture (98/2 by volume), 500 cm3 of a dichloromethane/-methanol mixture (96/4 by volume) and 1 dm3 of a dichloromethane/methanol mixture (90/10 by volume)
  9. additionThe fractions containing the expected product
  10. concentrationconcentrated under the above conditions

Sources & evidence

ORD record
ord-7594c154d5a8468497e3bb5a8ebbb102
Source dataset
uspto-grants-2002_09
Patent number
US06451821B1

Reaction notes

Loading…