o-Chlorophenylacetic acid → HCID 117720469, compound

HRID 1854580Notes

Reaction equation

HRID 1854580 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([OH:11])=O.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[OH:45][CH2:46][C@H:47]1[CH2:56][C:55]2[C:50](=[CH:51][CH:52]=[CH:53][C:54]=2[CH2:57][CH2:58][C:59]([CH3:62])([OH:61])[CH3:60])[C@H:49]([CH3:63])[NH:48]1>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]([N:48]1[C@@H:47]([CH2:46][OH:45])[CH2:56][C:55]2[C:50](=[CH:51][CH:52]=[CH:53][C:54]=2[CH2:57][CH2:58][C:59]([OH:61])([CH3:60])[CH3:62])[C@@H:49]1[CH3:63])=[O:11]

Participants

6

Reactant 4

HCID 17124o-Chlorophenylacetic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 117720356HCID 117720356, compound

Product 1

HCID 117720469HCID 117720469, compoundYield 33.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

Dissolve 2-(2-chlorophenyl)acetic acid (96.8 mg, 0.56 mmol) and O-(7-aza-1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (200 mg, 0.52 mmol) in dichloromethane (2 mL). Add diisopropylethylamine (183 μL, 1.05 mmol). Stir at ambient temperature for 20 min. Add this reaction mixture to a solution of 4-[(1S,3R)-3-(hydroxymethyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-5-yl]-2-methyl-butan-2-ol (92 mg, 0.35 mol) in dichloromethane (0.4 mL). Rinse with dichloromethane (1 mL) and stir at ambient temperature for 3.5 hours. Dilute the reaction mixture with water and stir. Extract with dichloromethane and dry the extracts over sodium sulfate, filter, and concentrate under reduced pressure. Purify the residue by silica gel chromatography, eluting with ethyl acetate: hexanes (gradient, 0-60%) to give a residue. Purify the residue by silica gel chromatography, eluting with 10% (2N ammonia in methanol): dichloromethane to give the title compound as a white foam (78 mg, 0.19 mmol). MS (m/z): 416.2 (M+1).

Workup

  1. washRinse with dichloromethane (1 mL)
  2. stirringstir at ambient temperature for 3.5 hours
  3. additionDilute the reaction mixture with water
  4. stirringstir
  5. extractionExtract with dichloromethane
  6. dry with materialdry the extracts over sodium sulfate
  7. filtrationfilter
  8. concentrationconcentrate under reduced pressure
  9. customPurify the residue by silica gel chromatography
  10. washeluting with ethyl acetate
  11. customhexanes (gradient, 0-60%) to give a residue
  12. customPurify the residue by silica gel chromatography
  13. washeluting with 10% (2N ammonia in methanol)

Sources & evidence

ORD record
ord-604e43803e664aa99b0e14bd078a9a0c
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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