Potassium Carbonate → (S)-4-nitrophenyl 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethylcarbamate

HRID 1993615Notes

Reaction equation

HRID 1993615 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@:8]([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)([NH2:16])[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1.[C:31](Cl)(=[O:42])[O:32][C:33]1[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=1.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:16][C:31](=[O:42])[O:32][C:33]2[CH:34]=[CH:35][C:36]([N+:39]([O-:41])=[O:40])=[CH:37][CH:38]=2)([C:17]2[CH:22]=[C:21]([O:23][C:24]([F:29])([F:28])[CH:25]([F:27])[F:26])[CH:20]=[C:19]([F:30])[CH:18]=2)[CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 821294-Nitrophenyl chloroformateHCID 59134703(S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethanamine

Product 1

HCID 59134633(S)-4-nitrophenyl 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethylcarbamate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethanamine (200 mg, 0.45 mmol) in DCM (2 mL) was added 4-nitrophenyl carbonochloridate (226.9 mg, 1.13 mmol) followed by the addition of K2CO3 (620.6 mg, 4.5 mmol). The reaction mixture was stirred at room temperature for 18 h and filtered through a small silica pad. The filtrate was diluted with DCM (20 mL), washed with saturated NaHCO3 (8×15 mL) till the aqueous layer only showed light yellow color. The organic layer was dried over MgSO4, filtered and concentrated to give (S)-4-nitrophenyl 1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethylcarbamate as a yellow oil (273 mg, crude 100%). This yellow oil was used directly to the next step without further purification. LCMS RT=2.213 min [M+H] 607.94 (Phenomenex Luna C18 column, 4.6×50 mm eluting with 10-90% MeOH/H2O over 2 minutes containing 0.1% TFA; 5 mL/min, monitoring at 220 nm)

Workup

  1. filtrationfiltered through a small silica pad
  2. additionThe filtrate was diluted with DCM (20 mL)
  3. washwashed with saturated NaHCO3 (8×15 mL) till the aqueous layer only showed light yellow color
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-84ef0ee4b9b44bc783f739ccb7047682
Source dataset
uspto-grants-2010_01
Patent number
US07652023B2

Reaction notes

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