Morpholine → 2-(3-{3-[(2-Chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-1-morpholinyl-ethanone hydrochloride salt

HRID 1296962Notes

Reaction equation

HRID 1296962 reaction equation
[Cl:1][C:2]1[C:37]([C:38]([F:41])([F:40])[F:39])=[CH:36][CH:35]=[CH:34][C:3]=1[CH2:4][N:5]([CH2:20][CH:21]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]([CH2:16][C:17]([OH:19])=O)[CH:13]=[CH:14][CH:15]=1.[NH:42]1[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC>CC#N>[ClH:1].[Cl:1][C:2]1[C:37]([C:38]([F:39])([F:40])[F:41])=[CH:36][CH:35]=[CH:34][C:3]=1[CH2:4][N:5]([CH2:20][CH:21]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]([CH2:16][C:17]([N:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[O:19])[CH:13]=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 4479053-(3-(((2-Chloro-3-(trifluoromethyl)phenyl)methyl)(2,2-diphenylethyl)amino)propoxy)benzeneacetic acid

Product 1

HCID 117651892-(3-{3-[(2-Chloro-3-(trifluoromethyl)-benzyl)-(2,2-diphenylethyl)-amino]-propoxy}phenyl)-1-morpholinyl-ethanone hydrochloride saltYield 108.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

2-(3-{3-[[2-chloro-3-(trifluoromethyl)benzyl)(2,2-diphenylethyl)-amino]-propoxy}-phenyl acetic acid (50 mg, 0.086 mmole) and morpholine (8.7 mg, 0.10 mmole) were dissolved in CH3CN (2 ml). BOP reagent (44 mg, 0.10 mmole) was added followed by Et3N (20 mg, 0.20 mmole). The resultant mixture was stirred at room temperature for 2 h. The mixture was concentrated under reduced pressure. The residue was partitioned between EtOAc and aqueous Na2CO3 (5%) solution. The organic layer was separated, dried over MgSO4 and concentrated. In cases where the product required further purification, a preparative Gilson HPLC was used (YMC CombiPrep ODS-A, 50×20 mm, 20 ml/min, 30–90% CH3CN over 15 minutes). The HCl salt was made by adding HCl (in ether) to an ether solution of the product and then evaporation of the solvent to give a yellow solid (32 mg, 54%). MS(ES) m/e 651.2 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customThe residue was partitioned between EtOAc and aqueous Na2CO3 (5%) solution
  3. customThe organic layer was separated
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customIn cases where the product required further purification
  7. custom(YMC CombiPrep ODS-A, 50×20 mm, 20 ml/min, 30–90% CH3CN over 15 minutes)
  8. additionby adding HCl (in ether) to an ether solution of the product
  9. customevaporation of the solvent

Sources & evidence

ORD record
ord-164752eb7b924d36a2149aa7bfefe7f9
Source dataset
uspto-grants-2007_07
Patent number
US07247748B2

Reaction notes

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