Oxalyl chloride → HCID 67211736, compound

HRID 1401886Notes

Reaction equation

HRID 1401886 reaction equation
[C:1]([O:5][C:6](=[O:34])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH2:29][CH2:28][C@@H:27]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:26][CH:25]=3)=[CH:20][CH:19]=2)[C:15](O)=[O:16])=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[Cl:41][C:42]1(N)[CH:47]=[CH:46][C:45]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)=[C:44]([CH3:54])[CH2:43]1.CC[N:58](C(C)C)C(C)C>ClCCl.CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:34])[C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH:14]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH2:29][CH2:28][C@@H:27]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH2:26][CH:25]=3)=[CH:20][CH:19]=2)[C:15](=[O:16])[NH:58][C:51]2[CH:52]=[CH:53][C:48]([C:45]3[CH:46]=[CH:47][C:42]([Cl:41])=[CH:43][C:44]=3[CH3:54])=[CH:49][CH:50]=2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 67211535HCID 67211535, compoundHCID 71238554HCID 71238554, compound

Product 1

HCID 67211736HCID 67211736, compoundYield 59%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4-{2-[4-(4-(R)-tert-Butylcyclohex-1-enyl)-phenyl]-2-carboxy-ethyl}-benzoic acid tert-butyl ester (697 mg, 1.51 mmol) in anhydrous dichloromethane (30 mL) was added oxalyl chloride (650 uL, 7.53 mmol) and 3 drops of DMF. The resulting solution was stirred at rt for 1 hr before being concentrated under vacuum. The residue was co-evaporated with toluene (1×5 mL) then dissolved in toluene again (20 mL). To the mixture was added 4-chloro-2-methylbiphenyl-4-ylamine (361 mg, 1.66 mmol) and DIPEA (1.3 mL, 7.53 mmol). The resulting mixture was refluxed for 90 min, diluted with ethyl acetate and washed with saturated NaHCO3. The organic portion was dried over Na2SO4 and concentrated under vacuum to afford crude material which was crystallized from MeOH to afford a white solid (590 mg). Removing the solvent and purification of the residue by chromatography on silica gel using an ethyl acetate/hexanes gradient afforded an additional 137 mg of product. 1H NMR (500 MHz, DMSO-d6): 10.16 (s, 1H), 7.78 (d, J=8 Hz, 2 H), 7.59 (d, J=8.5 Hz, 2 H), 7.4-7.32 (m, 7 H), 7.21 (d, J=8 Hz, 2 H), 7.15 (d, J=8 Hz, 2 H), 6.14 (m, 1H), 4.03 (dd, J=9, 7 Hz, 1 H), 3.48 (dd, J=13.5, 9.5 Hz, 1 H), 3.41 (dd, J=13.5, 6.5 Hz, 1 H), 2.4-2.3 (m, 1H), 2.2-2.15 (m, 4H), 1.96-1.9 (m, 2H), 1.52 (s, 9 H), 1.32-1.2 (m, 2 H), 0.89 (s, 9H).

Workup

  1. concentrationbefore being concentrated under vacuum
  2. dissolutionthen dissolved in toluene again (20 mL)
  3. temperatureThe resulting mixture was refluxed for 90 min
  4. washwashed with saturated NaHCO3
  5. dry with materialThe organic portion was dried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customto afford crude material which
  8. customwas crystallized from MeOH

Sources & evidence

ORD record
ord-8fc06f2a0adf4c2b8fa4e7c5a4146ca4
Source dataset
uspto-grants-2014_12
Patent number
US08907103B2

Reaction notes

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