Triphenylphosphine → 3-{3-[[2-Chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]-propoxy}-4-methyl-benzoic acid hydrochloride salt

HRID 229097Notes

Reaction equation

HRID 229097 reaction equation
C[O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7]([CH3:10])=[C:6]([OH:11])[CH:5]=1.[C:13]1([CH:19]([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH2:20][N:21]([CH2:34][CH2:35][CH2:36]O)[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[C:24]=2[Cl:33])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1(C)C=CC=CC=1>[ClH:33].[Cl:33][C:24]1[C:25]([C:29]([F:30])([F:31])[F:32])=[CH:26][CH:27]=[CH:28][C:23]=1[CH2:22][N:21]([CH2:20][CH:19]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)[C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:34][CH2:35][CH2:36][O:11][C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][C:7]=1[CH3:10])[C:3]([OH:2])=[O:12]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 354091Methyl 3-hydroxy-4-methylbenzoateHCID 5363146Diisopropyl azodicarboxylateHCID 577571173-[(2-Chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propan-1-ol

Product 1

HCID 688622453-{3-[[2-Chloro-3-(trifluoromethyl)benzyl](2,2-diphenylethyl)amino]-propoxy}-4-methyl-benzoic acid hydrochloride saltYield 103.2%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirring solution of 3-hydroxy-4-methyl-benzoic acid methyl ester (102 mg, 0.61 mmol) in anhydrous toluene (5 mL) was added N-(2,2-diphenylethyl)-N-(3-hydroxy-propyl)-N-(2-chloro-3-trifluoromethyl-benzyl)amine (211 mg, 0.47 mmol). Polymer bound triphenylphosphine (250 mg, 0.75 mmol, 3 mmol/g, Fluka Chemie) was then added, and the mixture stirred for 15 minutes. The reaction mixture was then cooled to 0° C. and diisopropylazodicarboxylate (115 ul, 0.58 mmol) was added in a dropwise fashion. After stirring at room temperature overnight, the crude reaction mixture was filtered and the resulting solid was washed with toluene. The filtrate was concentrated and the crude product was purified by preparative HPLC (TMC CombiPrep PDS, 75×30 mm, 25 mL/min, acetonitrile: H2O, UV detection at 254 nm) to give 150 mg (54% yield) of the title compound as a viscous oil. MS(ESI) 596.0(M+).

Workup

  1. additionwas then added
  2. stirringAfter stirring at room temperature overnight
  3. customthe crude reaction mixture
  4. filtrationwas filtered
  5. washthe resulting solid was washed with toluene
  6. concentrationThe filtrate was concentrated
  7. customthe crude product was purified by preparative HPLC (TMC CombiPrep PDS, 75×30 mm, 25 mL/min, acetonitrile: H2O, UV detection at 254 nm)

Sources & evidence

ORD record
ord-a9595c475e134ad5a39e07c081880178
Source dataset
uspto-grants-2009_07
Patent number
US07560586B2

Reaction notes

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