Potassium di-tert-butyl phosphate → HCID 72550900, compound

HRID 2206389Notes

Reaction equation

HRID 2206389 reaction equation
[Cl:1][C:2]1[C:3]([F:45])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:42]=[CH:41][C:34]([C:35]([O:37][CH2:38][CH2:39]I)=[O:36])=[CH:33][C:32]=2[O:43][CH3:44])=[O:29])[CH:5]=[CH:6][CH:7]=1.[C:46]([O:50][P:51]([O-:58])([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])([CH3:49])([CH3:48])[CH3:47].[K+]>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[C:3]([F:45])=[C:4]([C@@H:8]2[C@:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[C@H:11]([CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])[NH:10][C@H:9]2[C:28]([NH:30][C:31]2[CH:42]=[CH:41][C:34]([C:35]([O:37][CH2:38][CH2:39][O:58][P:51]([O:50][C:46]([CH3:49])([CH3:48])[CH3:47])([O:53][C:54]([CH3:55])([CH3:56])[CH3:57])=[O:52])=[O:36])=[CH:33][C:32]=2[O:43][CH3:44])=[O:29])[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 23674467Potassium di-tert-butyl phosphateHCID 72550899HCID 72550899, compound

Product 1

HCID 72550900HCID 72550900, compoundYield 54.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of chiral 2-iodoethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate (Example 11, 20 mg, 0.026 mmol) in dimethyl formamide (2 mL) was added potassium di-tert-butylphosphate (Accela ChemBio, 21.8 mg, 0.088 mmol). The reaction mixture was heated at 60° C. for 6 h. The mixture was diluted with ethyl acetate, washed with water and then brine, dried over anhydrous sodium sulfate and concentrated. The crude material was purified by flash chromatography to give chiral 2-(di-tert-butoxyphosphoryloxy)ethyl 4-((2R,3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-5-neopentylpyrrolidine-2-carboxamido)-3-methoxybenzoate (12 mg, 54% yield). MS (ES+) m/z calcd. for C41H50Cl2F2N3O8PNa: [(M+Na)+]: 874. found: 874.

Workup

  1. washwashed with water
  2. dry with materialbrine, dried over anhydrous sodium sulfate
  3. concentrationconcentrated
  4. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-08a5ccafb5394e6ab1401295db3c988d
Source dataset
uspto-grants-2016_06
Patent number
US09371280B2

Reaction notes

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