Triphenylphosphine → (1R)-N-(4-chloro-3-(1-(pyridin-2-yl)ethoxy)benzyl)-1-(3-chlorophenyl)ethanamine

HRID 1801606Notes

Reaction equation

HRID 1801606 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C@@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=2)[CH3:11])=[CH:4][C:3]=1[OH:19].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.[N:53]1[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=1[CH:59](O)[CH3:60]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C@@H:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=2)[CH3:11])=[CH:4][C:3]=1[O:19][CH:59]([C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][N:53]=1)[CH3:60]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 86784alpha-Methyl-2-pyridinemethanolHCID 59803158(R)-2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenol

Product 1

HCID 24954823(1R)-N-(4-chloro-3-(1-(pyridin-2-yl)ethoxy)benzyl)-1-(3-chlorophenyl)ethanamineYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of (R)-2-chloro-5-((1-(3-chlorophenyl)ethylamino)methyl)phenol 96 (130 mg, 439 μmol) in 5 mL of THF under N2 was added triphenylphosphine (127 mg, 483 μmol). The solution was chilled to 0° C. in an ice bath and then diisopropyl azodicarboxylate (94 μL, 483 μmol) was added dropwise to the reaction. After stirring for 15 min 0° C., a solution of 1-(pyridin-2-yl)ethanol (59 mg, 483 μmol) in THF was added to the reaction. The reaction was allowed to warm to room temperature and it was stirred for 10 h. The reaction was concentrated and diluted with EtOAc. The solution was extracted with saturated NaHCO3, water, and then brine. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. The crude material was purified by silica gel chromatography using a 5% to 90% gradient of EtOAc in hexanes as the eluant. The desired fractions were combined and concentrated to give (1R)—N-(4-chloro-3-(1-(pyridin-2-yl)ethoxy)benzyl)-1-(3-chlorophenyl)ethanamine 98 (67 mg, 38% yield) as a colorless oil and as a mixture of diastereomers. 1H NMR (400 MHz, d4-methanol) δ ppm 1.60 (d, J=6.65 Hz, 2.1H) 1.73 (d, J=5.28 Hz, 3H) 1.83 (d, J=6.46 Hz, 3H) 3.90 (d, J=11.15 Hz, 1H) 4.16 (d, J=12.72 Hz, 1H) 4.45-4.54 (m, 1H) 5.18-5.28 (m, 0.7H) 5.99 (m, 1H) 7.05 (d, 1H) 7.48 (m, 5H) 7.63 (m, 1H) 7.99 (m, 1.7H) 8.08 (m, 0.7H) 8.20 (d, 1H) 8.59 (m, 1.7H) 8.73 (m, 0.7H) 8.83 (d, 1H). Mass spectrum: calculated for C22H22Cl2N2O 401.3. found 402.4 (M++1).

Workup

  1. temperatureto warm to room temperature
  2. stirringit was stirred for 10 h
  3. concentrationThe reaction was concentrated
  4. additiondiluted with EtOAc
  5. extractionThe solution was extracted with saturated NaHCO3, water
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material was purified by silica gel chromatography
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-3a1c5b9a926e4161a2744087b6d53dc1
Source dataset
uspto-grants-2013_01
Patent number
US08349831B2

Reaction notes

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