Dimethylformamide → HCID 86671130, compound

HRID 476312Notes

Reaction equation

HRID 476312 reaction equation
[ClH:1].[C:2]1([CH:12]([NH:14][CH2:15][CH2:16][C@H:17]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=2)O)[CH3:13])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:31])=O.CN(C=O)C.CC(OC)(C)C>C1(C)C=CC=CC=1>[ClH:31].[Cl:1][C@@H:17]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=1)[CH2:16][CH2:15][NH:14][CH:12]([C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1)[CH3:13]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 15413tert-Butyl methyl etherHCID 24813Phosphorus oxychloride2×HCID 67052600(R)-3-(1-(naphthalen-1-yl)ethylamino)-1-(3-(trifluoromethyl)phenyl)propan-1-ol hydrochloride

Product 1

HCID 86671130HCID 86671130, compoundYield 28.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
60 °C

Procedure

(R)-3-(1-(naphthalen-1-yl)ethylamino)-1-(3-(trifluoromethyl)phenyl)propan-1-ol hydrochloride (IXa) (20.0 g, 48.796 mmol) is suspended in toluene (140 ml) at 40° C. and phosphoryl chloride (4.3 g, 28.044 mmol) is added drop-wise over 10 minutes. The reaction mixture is stirred two hours at 60° C., then DMF (1.0 g) is added at 40° C., followed by additional phosphoryl chloride (3.2 g, 20.870 mmol). The mixture is stirred at 40° C. overnight and then MTBE (40 ml) is added. Volatiles are removed by repeatedly distilling off under vacuum and restoring MTBE. After that a 1:1 vol/vol toluene/MTBE solution is received, which is heated up to 70° C. and allowed to cool down slowly to 15°-20° C. the so-obtained precipitate is aged at room temperature overnight, then filtered and washed with a 1:1 vol/vol toluene/MTBE mixture (3×12 ml). (R)-3-chloro-N-(1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine hydrochloride (X) is obtained as a white powder after exsiccation at 55° C. under vacuum (6.0 g, 14.008 mmol, yield: 28.7%).

Workup

  1. stirringThe mixture is stirred at 40° C. overnight
  2. customVolatiles are removed
  3. distillationby repeatedly distilling off under vacuum
  4. temperaturewhich is heated up to 70° C.
  5. temperatureto cool down slowly to 15°-20° C. the so-obtained precipitate
  6. waitis aged at room temperature overnight
  7. filtrationfiltered
  8. washwashed with a 1:1 vol/vol toluene/MTBE mixture (3×12 ml)

Sources & evidence

ORD record
ord-004b669eb7284c2c81ced5e0e41fa054
Source dataset
uspto-grants-2014_01
Patent number
US08637708B2

Reaction notes

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