Triethylamine → Methyl 3-[({[6-fluoro-3'-(hydroxymethyl)-3-biphenylyl]methyl}amino)-carbonyl]benzoate

HRID 564488Notes

Reaction equation

HRID 564488 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8]([OH:10])=O)=[O:4].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:38][CH2:39][C:40]1[CH:41]=[CH:42][C:43]([F:54])=[C:44]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([CH2:52][OH:53])[CH:47]=2)[CH:45]=1.C(N(CC)CC)C>C(Cl)Cl>[F:54][C:43]1[C:44]([C:46]2[CH:51]=[CH:50][CH:49]=[C:48]([CH2:52][OH:53])[CH:47]=2)=[CH:45][C:40]([CH2:39][NH:38][C:8]([C:7]2[CH:6]=[C:5]([CH:13]=[CH:12][CH:11]=2)[C:3]([O:2][CH3:1])=[O:4])=[O:10])=[CH:41][CH:42]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 6018803-(Methoxycarbonyl)benzoic acidHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 57813296[5'-(Aminomethyl)-2'-fluoro-3-biphenylyl]methanol

Product 1

HCID 57813353Methyl 3-[({[6-fluoro-3'-(hydroxymethyl)-3-biphenylyl]methyl}amino)-carbonyl]benzoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To 3-[(methyloxy)carbonyl]benzoic acid (0.18 g, 1 mmol) in CH2Cl2 (25 mL) was added HBTU (0.379 g, 1 mmol), followed by [5′-(aminomethyl)-2′-fluoro-3-biphenylyl]methanol (0.231 g, 1 mmol), and triethylamine (0.278 mL, 2 mmol). The mixture was stirred under argon overnight. The reaction mixture was then concentrated to dryness, and taken up in EtOAc and H2O. The organic phase was washed 2× with H2O, 1× with brine, dried and concentrated. The residue was absorbed on Isolute® Sorbent, and CombiFlashed on a 12 g column eluted with 0-100% EtOAc/hexane to afford the title compound as a white solid. LC-MS m/z 393.8 (M+H)+, 1.98 min (ret time); analytical HPLC shows 97.2% purity, (ret time 7.205 min).

Workup

  1. concentrationThe reaction mixture was then concentrated to dryness
  2. washThe organic phase was washed 2× with H2O, 1× with brine
  3. customdried
  4. concentrationconcentrated
  5. customThe residue was absorbed on Isolute® Sorbent, and CombiFlashed on a 12 g column
  6. washeluted with 0-100% EtOAc/hexane

Sources & evidence

ORD record
ord-02e14b9ffc5347d1bf35a923d2cff67a
Source dataset
uspto-grants-2011_11
Patent number
US08067408B2

Reaction notes

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