N-tert-butyl-N'-[(1R,2S)-1-(4-pyridylmethyl)-2-hydroxybutyl]thiourea → HCID 178463407, compound

HRID 47782Notes

Reaction equation

HRID 47782 reaction equation
[C:1]([NH:5][C:6]([NH:8][C@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)[C@@H:10](O)CC)=[S:7])(C)(C)[CH3:2]>Cl>[CH2:1]([NH:5][C:6]1[S:7][CH2:10][CH:9]([CH2:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[N:8]=1)[CH3:2]

Participants

3

Reactant 1

HCID 86584450N-tert-butyl-N'-[(1R,2S)-1-(4-pyridylmethyl)-2-hydroxybutyl]thiourea

Product 1

HCID 178463407HCID 178463407, compound

Reagents, catalysts & solvents 1

HCID 313Hydrochloric AcidSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 4.2 g of N-tert-butyl-N′-[(1R,2S)-1-(4-pyridylmethyl)-2-hydroxybutyl]thiourea in 40 cm3 of 6N hydrochloric acid is heated at a temperature in the region of 100° C. for 20 hours. After cooling to room temperature, the reaction mixture is concentrated under reduced pressure (1 kPa) at a temperature in the region of 50° C. The residue is chromatographed at atmospheric pressure on a column of silica gel (particle size 40-63μ; diameter 3.6 cm; height 24 cm), eluting with a dichloromethane/methanol mixture (98/2 by volume) and then with a dichloro-methane/methanol mixture (97/3 by volume). The fractions containing the expected product are combined and then concentrated under the above conditions, taken up in 30 cm3 of dichloromethane and basified with 1N sodium hydroxide. The organic phase is dried over magnesium sulfate, filtered and dried in a desiccator under reduced pressure (0.1 kPa) at a temperature in the region of 40° C. 1.4 g of (+)-(4R,5R)-5-(ethyl-4-(4-pyridylmethyl)-4,5-dihydro-2-thiazolylamine are obtained in the form of a white solid melting at 124° C. [1H NMR spectrum (300 MHz, (CD3)2SO-d6, δ in ppm): 0.83 (t, J=7.5 Hz: 3H); 1.43 (mt: 1H); 1.61 (mt: 1H); 2.70 (limiting AB: 2H); 3.40 (mt: 1H); 4.08 (mt: 1H); 6.28 (unresolved complex: 2H); 7.29 (broad d, J=5.5 Hz: 2H); 8.45 (broad d, J=5.5 Hz: 2H), (αD20=+166.9+/−2.4 at a concentration of 0.5% in methanol)].

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture is concentrated under reduced pressure (1 kPa) at a temperature in the region of 50° C
  3. customThe residue is chromatographed at atmospheric pressure on a column of silica gel (particle size 40-63μ; diameter 3.6 cm; height 24 cm)
  4. washeluting with a dichloromethane/methanol mixture (98/2 by volume)
  5. additionThe fractions containing the expected product
  6. concentrationconcentrated under the above conditions
  7. dry with materialThe organic phase is dried over magnesium sulfate
  8. filtrationfiltered
  9. customdried in a desiccator under reduced pressure (0.1 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-5f6a94e62fc84b658416f3dba66370cb
Source dataset
uspto-grants-2004_03
Patent number
US06699895B2

Reaction notes

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