Diphosgene → HCID 67001707, compound

HRID 561972Notes

Reaction equation

HRID 561972 reaction equation
[C:1]([O:5][C:6](=[O:34])[CH2:7][C@@H:8]([NH2:33])[C:9]([NH:11][C@H:12]([C:21]1[NH:22][C:23]([C:26]2[CH:31]=[CH:30][C:29]([I:32])=[CH:28][CH:27]=2)=[CH:24][N:25]=1)[C@H:13]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH3:14])=[O:10])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[O:44]=[C:45](Cl)OC(Cl)(Cl)Cl.C1(C)C=CC=CC=1.O1CCCC1>O1CCCC1>[C:1]([O:5][C:6](=[O:34])[CH2:7][C@@H:8]1[C:9](=[O:10])[N:11]([C@H:12]([C:21]2[NH:22][C:23]([C:26]3[CH:31]=[CH:30][C:29]([I:32])=[CH:28][CH:27]=3)=[CH:24][N:25]=2)[C@H:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH3:14])[C:45](=[O:44])[NH:33]1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 10426DiphosgeneHCID 81531DiisopropylethylamineHCID 22635083Tetrahydrofuran tolueneHCID 67001364HCID 67001364, compound

Product 1

HCID 67001707HCID 67001707, compoundYield 40.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

A solution of ((R)-3-amino-N-{(1S,2S)-1-[5-(4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-succinamic acid tert-butyl ester (400 mg, 0.7 mmol) in tetrahydrofuran (3 mL) containing N,N-diisopropylethylamine (0.37 mL, 2.1 mmol) was added via an addition funnel to diphosgene (0.059 mL, 0.49 mmol) in a 1:1 v/v mixture of toluene/tetrahydrofuran (6 mL) at −40° C. under an atmosphere of nitrogen with stirring. The reaction was stirred at this temperature for 20 minutes and then allowed to warm to 10° C. before quenching with ice/water (5 mL). After stirring for 2 minutes the mixture was extracted with ethyl acetate (2×25 mL). The organic extracts were combined, washed with water (2×10 mL), brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted with 0 to 50% v/v ethyl acetate/hexanes to give ((R)-1-{(1S,2S)-1-[5-(4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-2,5-dioxo-imidazolidin-4-yl)-acetic acid tert-butyl ester (120 mg, 29%). LC-MS: calcd for C27H29IN4O4 [M+H+] 601. Found 601

Workup

  1. stirringThe reaction was stirred at this temperature for 20 minutes
  2. custombefore quenching with ice/water (5 mL)
  3. stirringAfter stirring for 2 minutes the mixture
  4. extractionwas extracted with ethyl acetate (2×25 mL)
  5. washwashed with water (2×10 mL), brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by chromatography over silica gel gradient
  10. washeluted with 0 to 50% v/v ethyl acetate/hexanes

Sources & evidence

ORD record
ord-43ec6caa7525457f96496cdf05711c2a
Source dataset
uspto-grants-2011_11
Patent number
US08063085B2

Reaction notes

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