Methanol → HCID 90001056, compound

HRID 1496818Notes

Reaction equation

HRID 1496818 reaction equation
[CH2:1]([CH:3]1[O:5][CH2:4]1)Cl.[CH2:6]([C:8]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[C:9]=1[NH2:10])[CH3:7].[OH-:16].[K+].[CH3:18]O>>[CH2:6]([C:8]1[CH:14]=[CH:13][CH:12]=[C:11]([CH3:15])[C:9]=1[NH:10][CH2:18][C@@H:1]([OH:16])[CH2:3][O:5][CH3:4])[CH3:7]

Participants

5

Reactant 4

HCID 887Methanol2×HCID 7835EpichlorohydrinHCID 14797Potassium HydroxideHCID 324852-Ethyl-6-methylaniline

Product 1

HCID 90001056HCID 90001056, compoundYield 96%

Conditions

Temperature
70 °C

Procedure

To a stirred solution of epichlorohydrin (R)-2 (2 g, 21.6 mmol) in methanol (15 mL) was added 2-ethyl-6-methyl aniline (3.2 g, 23.7 mmol) and the resulting mixture was refluxed for 6 h at 70° C. After completion of the reaction (monitored by TLC), crushed KOH (3.0 g, 54.0 mmol) was added portion wise at temperature 10° C. After completing the addition, the reaction mixture was stirred vigorously for 8 h at 30° C. After completion of the reaction (monitored by TLC), excess methanol was evaporated under reduced pressure. The reaction mixture was then poured into water (20 mL) and extracted with EtOAc (2×15 mL). The combined organic layers were washed with brine (10 mL) and dried over Na2SO4. Evaporation of the solvent gave the crude residue which was purified by silica gel column chromatography using petroleum ether/EtOAc (90:10) as eluent to furnish (R)-1((2-ethyl-6-methylphenyl)amino)-3-methoxypropan-2-ol (R)-3 as a pale brown oil (4.6 g, 96%); [α]21D=+4.93 (c 2.09, CHCl3); IR (CHCl3, cm−1): νmax 3421, 3009, 2966, 1593, 1466, 1377, 1216, 1129, 968, 667; 1H NMR (400 MHz, CDCl3): δH 1.26 (t, J=7.5 Hz, 3H), 2.33 (s, 3H), 2.66-2.71 (m, 2H), 2.96-3.00 (dd, J=12.4, 7 Hz, 1H), 3.09-3.12 (dd, J=12.4, 3.9 Hz, 1H), 3.42 (s, 3H), 3.46-3.49 (dd, J=9.4, 6.3 Hz, 1H), 3.50-3.53 (dd J=9.7, 3.6 Hz, 1H), 3.96-4.00 (m, 1H), 6.91 (apparent t, J=7.2 Hz, 1H), 7.01 (d, J=7.3 Hz, 1H), 7.04 (d, J=7.6 Hz, 1H); 13C NMR (100 Hz, CDCl3): δC 145, 136.2, 130.6, 128.8, 126.7, 122.6, 75.3, 69.6, 59.2, 51.5, 24.2, 18.5, 14.8; MS: m/z 224 [M+1]+, 246 [M+Na]+.

Workup

  1. customAfter completion of the reaction (monitored by TLC)
  2. additionwas added portion wise at temperature 10° C
  3. additionthe addition
  4. customwas evaporated under reduced pressure
  5. additionThe reaction mixture was then poured into water (20 mL)
  6. extractionextracted with EtOAc (2×15 mL)
  7. washThe combined organic layers were washed with brine (10 mL)
  8. dry with materialdried over Na2SO4
  9. customEvaporation of the solvent
  10. customgave the crude residue which
  11. customwas purified by silica gel column chromatography

Sources & evidence

ORD record
ord-1a08bd468a6240d38bf16f479fc89241
Source dataset
uspto-grants-2015_12
Patent number
US09199930B2

Reaction notes

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