2-Chloro-4-fluorobenzoic acid → HCID 67773169, compound

HRID 1808852Notes

Reaction equation

HRID 1808852 reaction equation
CCN(C(C)C)C(C)C.[Cl:10][C:11]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH:43]1([C@H:47]([NH:54][CH3:55])[CH2:48][N:49]2[CH2:52][CH:51]([OH:53])[CH2:50]2)[CH2:46][CH2:45][CH2:44]1>C(Cl)Cl>[Cl:10][C:11]1[CH:19]=[C:18]([F:20])[CH:17]=[CH:16][C:12]=1[C:13]([N:54]([C@@H:47]([CH:43]1[CH2:46][CH2:45][CH2:44]1)[CH2:48][N:49]1[CH2:50][CH:51]([OH:53])[CH2:52]1)[CH3:55])=[O:15]

Participants

6

Reactant 4

HCID 752592-Chloro-4-fluorobenzoic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67772265HCID 67772265, compound

Product 1

HCID 67773169HCID 67773169, compoundYield 51.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

DIPEA (0.183 mL, 1.05 mmol) was added to a stirred suspension of 2-chloro-4-fluorobenzoic acid (55 mg, 0.31 mmol) and TBTU (0.101 g, 0.31 mmol) in DCM (1 mL) at rt. The suspension was stirred for 5 min before it was cooled on an ice-bath. A solution of (S)-1-(2-cyclobutyl-2-(methylamino)ethyl)azetidin-3-ol (Compound Z2.1) (0.07 g, 0.35 mmol) in DCM (1 mL) was added over 3 min. The ice-bath was removed and the reaction was stirred at rt for 2 h. The reaction mixture was washed with NaHCO3 (8% aq., 3 mL), filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC to give the title compound (54 mg, 45%). Mixture of rotamers: 1H NMR (600 MHz, DMSO-d6) δ 1.41-2.1, 2.22-2.85, 3.06-3.59, 4.02-4.23, 4.46-4.60, 5.17-5.35, 7.23-7.72. HRMS (M+H)+: calculated 341.1432. found 341.1442.

Workup

  1. temperaturewas cooled on an ice-bath
  2. customThe ice-bath was removed
  3. stirringthe reaction was stirred at rt for 2 h
  4. washThe reaction mixture was washed with NaHCO3 (8% aq., 3 mL)
  5. filtrationfiltered through a phase separator
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-525c0068a96f4d3ea20204805602660c
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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