Diisopropylethylamine → HCID 86641223, compound

HRID 1958725Notes

Reaction equation

HRID 1958725 reaction equation
CNC1C=[CH:7][C:6]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:5]C=1.ClC(Cl)([O:19]C(=O)OC(Cl)(Cl)Cl)Cl.C[CH2:29][N:30]([CH:34](C)C)[CH:31]([CH3:33])[CH3:32].FC(F)(F)C([O-])=O.[NH2:44][C@H:45]([CH2:50][C:51]([O:53][CH2:54][C:55]1[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=1)=[O:52])[CH2:46][NH+:47]([CH3:49])[CH3:48]>C1COCC1>[CH3:49][N:47]([CH3:48])[CH2:46][C@H:45]([NH:44][C:34]([N:30]([CH3:29])[C:31]1[CH:32]=[CH:5][C:6]([O:9][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:7][CH:33]=1)=[O:19])[CH2:50][C:51]([O:53][CH2:54][C:55]1[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=1)=[O:52]

Participants

6

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 21706442N-methyl-4-phenoxyanilineHCID 68743121HCID 68743121, compound

Product 1

HCID 86641223HCID 86641223, compoundYield 139.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of N-methyl-4-phenoxyaniline (110 mg, 0.55 mmol) in anh THF (10 mL) under Ar was added triphosgene (60 mg, 0.20 mmol) in one portion at 0° C. followed by DIPEA (0.1 mL, 0.58 mmol). The reaction was stirred at the temperature for 10 min and then at rt for 2 h. At this time, the reaction was cooled and treated with (R)-2-amino-4-(benzyloxy)-N,N-dimethyl-4-oxobutan-1-aminium 2,2,2-trifluoroacetate (193 mg, 0.55 mmol) in anh THF (6 mL) at 0° C. followed by DIPEA (0.3 mL, 1.7 mmol). The reaction was allowed to slowly warm to rt overnight. The mixture was then concentrated under reduced pressure and purified by preparative TLC (SiO2, 20% MeOH/DCM) to afford the title compound as a light yellow oil (129 mg, 51%). 1H NMR (400 MHz, CD3OD) δ ppm 7.22-7.42 (m, 8 H), 7.08-7.19 (m, 3 H), 7.00-7.06 (m, 2 H), 6.90-6.95 (m, 2 H), 5.05-5.20 (m, 2 H), 4.50-4.62 (m, 1 H), 3.19 (s, 3 H), 2.99-3.17 (m, 2 H), 2.86 (s, 6 H), 2.50-2.71 (m, 2 H). MS ESI [M+H]+, calcd for [C27H31N3O4+H]+: 462.56 found m/z 462.3 (100).

Workup

  1. waitat rt for 2 h
  2. temperatureAt this time, the reaction was cooled
  3. concentrationThe mixture was then concentrated under reduced pressure
  4. custompurified by preparative TLC (SiO2, 20% MeOH/DCM)

Sources & evidence

ORD record
ord-c197e251ba7d4dab936b4b7ea734679c
Source dataset
uspto-grants-2013_04
Patent number
US08410150B2

Reaction notes

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