Dimethylformamide → HCID 18993087, compound

HRID 375631Notes

Reaction equation

HRID 375631 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C=O)C.C(Cl)(=O)C(Cl)=O.[NH:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[CH:32]=[C:31]1[Zn]>C(Cl)(Cl)Cl>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:11]=[CH:12][C:13]([C:14]([C:32]2[C:33]3[C:38](=[CH:37][CH:36]=[CH:35][CH:34]=3)[NH:30][CH:31]=2)=[O:16])=[CH:17][CH:18]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 8536054-(((tert-Butoxycarbonyl)amino)methyl)benzoic acidHCID 178528052HCID 178528052, compound

Product 1

HCID 18993087HCID 18993087, compoundYield 43.8%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a 0° C. solution of 4-(N-tert-butoxycarbonylaminomethyl)benzoic acid (5.07 g, 20.2 mmol) in CHCl3 was added DMF (200 μL) and oxalyl chloride (1.94 mL, 22.2 mmol). The cold bath was removed and the reaction mixture was stirred for 2 hours at ambient temperature, after which it was concentrated in vacuo. The residue was taken up in CH2Cl2 and added to a solution of indolylzinc (50.5 mmol, prepared as described in Example 1, step 4, except substituting indole for 6-(4-fluorophenyl)indole). The reaction mixture was stirred for 16 hours at ambient temperature, then quenched with saturated aqueous NH4Cl and partitioned between CH2Cl2 and saturated aqueous NH4Cl. The solids were filtered off and rinsed with CH2Cl2. The layers were separated and the organic phase was dried over MgSO4, filtered, and concentrated in vacuo. Pure 3-[4-(N-tert-butoxycarbonylaminomethyl)benzoyl]indole (3.10 g) was obtained by chromatography on silica gel (60% ether/hexanes, then 60% ethyl acetate/hexanes).

Workup

  1. customThe cold bath was removed
  2. concentrationafter which it was concentrated in vacuo
  3. stirringThe reaction mixture was stirred for 16 hours at ambient temperature
  4. customquenched with saturated aqueous NH4Cl
  5. custompartitioned between CH2Cl2 and saturated aqueous NH4Cl
  6. filtrationThe solids were filtered off
  7. washrinsed with CH2Cl2
  8. customThe layers were separated
  9. dry with materialthe organic phase was dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-725e1bac1be6478daa5e1367d171a0b4
Source dataset
uspto-grants-1996_01
Patent number
US05486525

Reaction notes

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