Water → N,N-Dimethyl-3-((naphthalen-1-yl)oxy)-3-(thiophen-2-yl)propan-1-amine

HRID 2388360Notes

Reaction equation

HRID 2388360 reaction equation
[CH3:1][N:2]([CH3:12])[CH2:3][CH2:4][CH:5]([C:7]1[S:8][CH:9]=[CH:10][CH:11]=1)[OH:6].[NH2-].[Na+].F[C:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][CH:17]=1.O>CS(C)=O.C(O)(=O)C>[CH3:12][N:2]([CH3:1])[CH2:3][CH2:4][CH:5]([O:6][C:24]1[C:25]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:21]=[CH:22][CH:23]=1)[C:7]1[S:8][CH:9]=[CH:10][CH:11]=1

Participants

7

Reactant 4

HCID 962WaterHCID 94501-FluoronaphthaleneHCID 24533Sodium amideHCID 115864093-(Dimethylamino)-1-(2-thienyl)-1-propanol

Product 1

HCID 11573192N,N-Dimethyl-3-((naphthalen-1-yl)oxy)-3-(thiophen-2-yl)propan-1-amine

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
87.5 °C

Procedure

N,N-dimethyl-3-(2-thienyl)-3-hydroxypropanamine (2, racemic hydroxy compound) (50 gm) was dissolved in dimethyl sulfoxide (250 ml). To the clear solution sodamide (13.7 gm) was added at 20-25° C. in small lots within 10-15 minutes under nitrogen atmosphere. The resulting reaction mass was stirred for half an hour to get a clear solution. To this solution 1-fluoronaphthalene (3) (43.4 gm) was added in 20-25 minutes. The temperature was raised to 80-95° C. and stirred for 3-5 hours, then cooled to 25-30° C. Reaction mass added into cold-water (500 ml), pH was adjusted to 5.5-6.0 with acetic acid. Aqueous reaction mass washed with cyclohexane followed by pH adjustment between 10.5-11.0 with caustic solution. Reaction mixture was extracted with cyclohexane and organic layer concentrated under reduced pressure to provide thick oily mass of (±)-N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine (4). The oily mass was dissolved in ethyl acetate (250 ml) and oxalic acid (30 gm) was added. Stirred at 50-60° C. for 1 hour then at 25-30° C. for 2 hours. Solid was filtered and dried to give racemic N,N-dimethyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine oxalate (5, HA=oxalic acid) as white solid. Yield: 75 gm.

Workup

  1. customThe resulting reaction mass
  2. customto get a clear solution
  3. stirringstirred for 3-5 hours
  4. temperaturecooled to 25-30° C
  5. customReaction mass
  6. washAqueous reaction mass washed with cyclohexane
  7. customReaction mixture
  8. extractionwas extracted with cyclohexane and organic layer
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0e40e8b7ac384347b7d8a53997a0ec97
Source dataset
uspto-grants-2012_09
Patent number
US08269023B2

Reaction notes

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