Phosgene → HCID 118098725, compound

HRID 708847Notes

Reaction equation

HRID 708847 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([CH2:13][CH3:14])[C:9]([O:11][CH3:12])=[O:10])=[C:4]([CH2:15][N:16]([CH3:58])[C:17](=[O:57])[CH:18]([NH:30][C:31]2[CH:32]=[C:33]3[C:38](=[CH:39][CH:40]=2)[C:37]([N:41]([C:49]([O:51][C:52]([CH3:55])([CH3:54])[CH3:53])=[O:50])[C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[N:36][CH:35]=[C:34]3[F:56])[C:19]2[CH:24]=[CH:23][C:22]([C@@H:25]([CH3:28])[CH2:26][OH:27])=[C:21]([CH3:29])[CH:20]=2)[CH:3]=1.[C:59](Cl)(Cl)=[O:60]>C(#N)C.ClCCl>[C:52]([O:51][C:49]([N:41]([C:42]([O:44][C:45]([CH3:48])([CH3:46])[CH3:47])=[O:43])[C:37]1[C:38]2[C:33](=[CH:32][C:31]([NH:30][C@H:18]3[C:17](=[O:57])[N:16]([CH3:58])[CH2:15][C:4]4[CH:3]=[C:2]([CH:7]=[CH:6][C:5]=4[C@@H:8]([CH2:13][CH3:14])[C:9]([O:11][CH3:12])=[O:10])[NH:1][C:59](=[O:60])[O:27][CH2:26][C@H:25]([CH3:28])[C:22]4[CH:23]=[CH:24][C:19]3=[CH:20][C:21]=4[CH3:29])=[CH:40][CH:39]=2)[C:34]([F:56])=[CH:35][N:36]=1)=[O:50])([CH3:55])([CH3:54])[CH3:53]

Participants

5

Reactant 2

HCID 6371PhosgeneHCID 131733865HCID 131733865, compound

Product 1

HCID 118098725HCID 118098725, compoundYield 47.3%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of 13F (235 mg, 0.293 mmol) in acetonitrile (4 mL) and dichloromethane (2 mL) was cooled to 0° C. To this solution was added phosgene (20% in toluene, 0.159 mL, 0.322 mmol). The mixture was stirred at 0° C. for 5 min, and rt for 1 h. The mixture was bubbled with Ar for 10 min to remove excess phosgene. The resulting solution was added dropwise over 3 h via a syringe pump into a solution of TEA (0.408 mL, 2.93 mmol) in CH2Cl2 (100 mL) at rt. The solution was stirred at rt for 16 h. The reaction mixture was concentrated and purified by flash chromatography to give a mixture of diastereoisomers (198 mg, 82% yield). The diastereoisomers (169 mg, 0.204 mmol) were separated by a prep chiral HPLC to give 13G (80 mg, 47.3% yield). MS (ESI) m/z: 827.9 (M+H)+.

Workup

  1. waitrt for 1 h
  2. customThe mixture was bubbled with Ar for 10 min
  3. customto remove excess phosgene
  4. stirringThe solution was stirred at rt for 16 h
  5. concentrationThe reaction mixture was concentrated
  6. custompurified by flash chromatography
  7. customto give
  8. additiona mixture of diastereoisomers (198 mg, 82% yield)
  9. customThe diastereoisomers (169 mg, 0.204 mmol) were separated by a prep chiral HPLC

Sources & evidence

ORD record
ord-5a9f5e6fe095409ba1f549adf06e19f0
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

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