Ammonia → HCID 59497921, compound

HRID 1676136Notes

Reaction equation

HRID 1676136 reaction equation
[OH:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH2:9][CH2:10][C:11]([C:13]2[S:14][CH:15]=[C:16]([CH2:19][CH:20]([CH3:22])[CH3:21])[C:17]=2[CH3:18])=[O:12])=[CH:4][C:3]=1[CH3:23].[CH2:24]([CH:26]1[O:28][CH2:27]1)Cl.[NH3:29]>C(O)(C)C.[OH-].[Na+].C([O-])(O)=O.[Na+].CO>[NH2:29][CH2:24][CH:26]([OH:28])[CH2:27][O:1][C:2]1[C:7]([CH3:8])=[CH:6][C:5]([CH2:9][CH2:10][C:11]([C:13]2[S:14][CH:15]=[C:16]([CH2:19][CH:20]([CH3:21])[CH3:22])[C:17]=2[CH3:18])=[O:12])=[CH:4][C:3]=1[CH3:23]

Participants

8

Reactant 3

HCID 222AmmoniaHCID 7835EpichlorohydrinHCID 59497942HCID 59497942, compound

Product 1

HCID 59497921HCID 59497921, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 3776IsopropanolSolventHCID 14798Sodium HydroxideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 3-(4-hydroxy-3,5-dimethyl-phenyl)-1-(4-isobutyl-3-methyl-thiophen-2-yl)-propan-1-one (317 mg, 0.96 mmol) in isopropanol (10 mL), 3 N aq. NaOH (2.5 mL) followed by epichlorohydrine (284 mg, 3.07 mmol) is added. The dark red mixture is stirred at rt for 16 h before it is diluted with sat. aq. NaHCO3 and extracted twice with diethyl ether. The organic extracts are washed with water, dried over Na2SO4, filtered and evaporated to give crude 3-(3,5-dimethyl-4-oxiranylmethoxy-phenyl)-1-(4-isobutyl-3-methyl-thiophen-2-yl)-propan-1-one (339 mg) as a yellow oil. The material is dissolved in 7 N NH3 in methanol (7.5 mL) and the resulting solution is stirred in an autoklave at 65° C. for 2.5 h. The solvent is removed in vacuo and the residue is dried under HV to leave rac-3-[4-(3-amino-2-hydroxy-propoxy)-3,5-dimethyl-phenyl]-1-(4-isobutyl-3-methyl-thiophen-2-yl)-propan-1-one (353 mg) as an orange oil; LC-MS: tR=0.88 min, [M+1]=404.20; 1H NMR (CDCl3): δ 7.06 (s, 1H), 6.88 (s, 2H), 3.98-3.90 (m 1H), 3.85-3.73 (m, 2H), 3.15-3.07 (m, 2H), 3.00-2.84 (m, 4H), 2.47 (s, 3H), 2.42 (d, J=7.6 Hz, 2H), 2.25 (s, 6H), 1.83 (hept, J=7.0 Hz, 1H), 0.92 (d, J=6.4 Hz, 6H).

Workup

  1. additionis added
  2. extractionextracted twice with diethyl ether
  3. washThe organic extracts are washed with water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated
  7. customto give crude 3-(3,5-dimethyl-4-oxiranylmethoxy-phenyl)-1-(4-isobutyl-3-methyl-thiophen-2-yl)-propan-1-one (339 mg) as a yellow oil
  8. stirringthe resulting solution is stirred in an autoklave at 65° C. for 2.5 h
  9. customThe solvent is removed in vacuo
  10. customthe residue is dried under HV

Sources & evidence

ORD record
ord-2459e3e669a34e089f08cb26f4f32782
Source dataset
uspto-grants-2011_08
Patent number
US08003800B2

Reaction notes

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