Hydrochloric Acid → HCID 68548579, compound

HRID 2242565Notes

Reaction equation

HRID 2242565 reaction equation
[ClH:1].CNCC(O)C(N(C)C1C=CC(C)=CC=1)C1C=CC=CC=1.C=O.[OH-].[Na+].[CH3:27][N:28]([CH3:48])[CH2:29][CH:30]([OH:47])[CH:31]([N:38]([CH3:46])[C:39]1[CH:44]=[CH:43][C:42]([CH3:45])=[CH:41][CH:40]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.Cl>C(O)=O.C(O)C.O>[ClH:1].[CH3:48][N:28]([CH3:27])[CH2:29][CH:30]([OH:47])[CH:31]([N:38]([CH3:46])[C:39]1[CH:40]=[CH:41][C:42]([CH3:45])=[CH:43][CH:44]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 14798Sodium HydroxideHCID 24897031HCID 24897031, compoundHCID 68551856HCID 68551856, compound

Product 1

HCID 68548579HCID 68548579, compoundYield 75%

Reagents, catalysts & solvents 3

HCID 284Formic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
70 °C

Procedure

To a mixture of (1RS,2SR)-3-(methylamino)-1-[methyl(4-methylphenyl)amino]-1-phenylpropan-2-ol hydrochloride (Example 12, 83 mg, 0.23 mmol) in formic acid (0.4 mL) at 50° C., was added an aqueous solution of formaldehyde (37% in water, 0.16 mL). The reaction was heated at 70° C. for 1 hour, then poured into water (10 mL) and basified to pH 10 with the addition of an aqueous solution of sodium hydroxide (2 N). The product was extracted with ethyl acetate (3×10 mL), and the combined organic extracts were dried (anhydrous sodium sulfate) and concentrated to yield 59 mg (86%) 1RS,2SR)-3-(dimethylamino)-1-[methyl(4-methylphenyl)amino]-1-phenylpropan-2-ol as a viscous, colorless liquid. The product was dissolved in ethanol (0.5 mL) and treated with a solution of hydrochloric acid (0.1 mL, 4 M in 1,4-dioxane). All volatiles were again removed under reduced pressure. The resulting white solid was recrystallized (isopropanol/ethyl ether/−20° C.) to yield 64 mg (75%) of (1RS,2SR)-3-(dimethylamino)-1-[methyl(4-methylphenyl)amino]-1-phenylpropan-2-ol hydrochloride as a white powder. MS (ESI) m/z 299.1 ([M−H]+); HRMS: calculated for C19H26N2O+H, 299.2118; found (ESI, [M+H]+), 299.2109.

Workup

  1. extractionThe product was extracted with ethyl acetate (3×10 mL)
  2. dry with materialthe combined organic extracts were dried (anhydrous sodium sulfate)
  3. concentrationconcentrated
  4. customto yield 59 mg (86%)
  5. customAll volatiles were again removed under reduced pressure
  6. customThe resulting white solid was recrystallized (isopropanol/ethyl ether/−20° C.)

Sources & evidence

ORD record
ord-6fb4acfbb13b49258d63abbe22e9e6a3
Source dataset
uspto-grants-2010_03
Patent number
US07671238B2

Reaction notes

Loading…