4-Chlorophenol → HCID 66739481, compound

HRID 1402741Notes

Reaction equation

HRID 1402741 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.ClC(Cl)(O[C:13](=[O:19])OC(Cl)(Cl)Cl)Cl.CCN(C(C)C)C(C)C.[NH:30]1[CH2:33][CH:32]([C:34]([N:36]2[CH2:42][CH2:41][CH2:40][N:39]([CH:43]3[CH2:46][CH2:45][CH2:44]3)[CH2:38][CH2:37]2)=[O:35])[CH2:31]1>ClCCCl.C(Cl)Cl.O>[CH:43]1([N:39]2[CH2:40][CH2:41][CH2:42][N:36]([C:34]([CH:32]3[CH2:31][N:30]([C:13]([O:8][C:5]4[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=4)=[O:19])[CH2:33]3)=[O:35])[CH2:37][CH2:38]2)[CH2:46][CH2:45][CH2:44]1

Participants

8

Reactant 4

HCID 46844-ChlorophenolHCID 81531DiisopropylethylamineHCID 94429TriphosgeneHCID 667393581-(Azetidin-3-ylcarbonyl)-4-cyclobutyl-1,4-diazepane

Product 1

HCID 66739481HCID 66739481, compoundYield 0.2%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A stirred solution of 4-chlorophenol (200 mg, 1.56 mmol) and triphosgene (460 mg, 1.56 mmol) in DCE (5 ml) was cooled to 0° C. and DIPEA (2.16 ml, 12.4 mmol) added. The resulting solution was stirred at 0° C. for 90 minutes then 1-(azetidin-3-ylcarbonyl)-4-cyclobutyl-1,4-diazepane (367 mg, 1.56 mmol) in DCE (2 ml) was added. The resulting mixture was heated at 100° C. for 12 hours then cooled to room temperature and diluted with DCM (25 ml) and water (30 ml). The organic phase was separated and the aqueous phase extracted with DCM (3×25 ml). The organics were combined, dried (MgSO4), filtered and concentrated at reduced pressure. The residue was purified by FCC (98:2:1 DCM:MeOH:NH3) followed by preparative HPLC (Method 2) to yield the title compound (1.4 mg, 0.2% yield).

Workup

  1. temperatureThe resulting mixture was heated at 100° C. for 12 hours
  2. temperaturethen cooled to room temperature
  3. customThe organic phase was separated
  4. extractionthe aqueous phase extracted with DCM (3×25 ml)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated at reduced pressure
  8. customThe residue was purified by FCC (98:2:1 DCM:MeOH:NH3)

Sources & evidence

ORD record
ord-e4e988e885414280a1a37ae285dfa966
Source dataset
uspto-grants-2014_12
Patent number
US08912176B2

Reaction notes

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