4-Chlorobenzoic Acid → HCID 57345436, compound

HRID 1808850Notes

Reaction equation

HRID 1808850 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:42][NH:43][C@H:44]([CH2:51][CH2:52][CH3:53])[CH2:45][N:46]1[CH2:49][CH:48]([OH:50])[CH2:47]1.[OH-].[K+]>C(Cl)Cl.C1COCC1.CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([N:43]([C@H:44]([CH2:51][CH2:52][CH3:53])[CH2:45][N:46]2[CH2:47][CH:48]([OH:50])[CH2:49]2)[CH3:42])=[O:8])=[CH:9][CH:10]=1

Participants

9

Reactant 5

HCID 63184-Chlorobenzoic AcidHCID 14797Potassium HydroxideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67772493HCID 67772493, compound

Product 1

HCID 57345436HCID 57345436, compoundYield 73.2%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

4-chlorobenzoic acid (0.527 g, 3.37 mmol) and DIPEA (1.176 mL, 6.73 mmol) were mixed in DCM (20 mL) at 0° C. After stirring for 10 min, TBTU (1.103 g, 3.43 mmol) was added to the reaction mixture. The mixture was stirred at 0° C. for 20 min. The above mixture was added in three portions to a solution of (R)-1-(2-(methylamino)pentyl)-azetidin-3-ol (Compound G2.5) (0.58 g, 3.37 mmol) in DCM (20 mL) within 10 min at 0° C. The mixture was stirred at 0° C. for 2.5 h, then warmed to rt and the mixture was stirred overnight. The mixture was concentrated to dryness. To the residue was added aq KOH (30 mL, 15.00 mmol) and methanol (15 mL)/THF (15 mL). The reaction mixture was stirred at rt for 2.5 h. The mixture was concentrated and extracted with DCM (30 mL×2). The DCM layers were combined, evaporated in vacuo to an oil residue. The crude was purified by preparative HPLC to afford the title compound (0.766 g, 73.2%). Mixture of rotamers:

Workup

  1. stirringThe mixture was stirred at 0° C. for 20 min
  2. stirringThe mixture was stirred at 0° C. for 2.5 h
  3. stirringthe mixture was stirred overnight
  4. concentrationThe mixture was concentrated to dryness
  5. stirringThe reaction mixture was stirred at rt for 2.5 h
  6. concentrationThe mixture was concentrated
  7. extractionextracted with DCM (30 mL×2)
  8. customevaporated in vacuo to an oil residue
  9. customThe crude was purified by preparative HPLC

Sources & evidence

ORD record
ord-d8ba37a25a7c46c3a32e3a84a4c1683b
Source dataset
uspto-grants-2013_01
Patent number
US08361998B2

Reaction notes

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