Carbon dioxide methanol → HCID 90088627, compound

HRID 2276863Notes

Reaction equation

HRID 2276863 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[C:10]=3[NH:11][C:12](=[O:26])[CH:13]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:14]=2)[CH:5]=[CH:6][CH:7]=1.C(=O)=O.CO>>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[C:10]=3[NH:11][C:12](=[O:26])[C@@H:13]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:14]=2)[CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 21973728Carbon dioxide methanolHCID 90088631HCID 90088631, compound

Product 1

HCID 90088627HCID 90088627, compoundYield 46%

Procedure

Racemic benzyl (5-(3-fluorophenyl)-9-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)carbamate (5.9 g, 14.3 mmol) was resolved under the Chiral SFC conditions. Berger SFC MGIII, Column: CHIRALPAK® IC 25×3 cm ID, 5 μm, Mobile Phase: 45/55 CO2/MeOH; Flow rate: 160 mL/min; Detector wavelength: 220 nM. The desired stereoisomer was collected as the second peak in the elution order. After evaporation of solvent, (S)-benzyl (5-(3-fluorophenyl)-9-methyl-2-oxo-2,3-dihydro-1H-benzo[e][1,4]diazepin-3-yl)carbamate (2.73 g, 46% yield) was obtained as a white solid. HPLC: RT=3.075 min Purity=99%. (H2O/MeOH with TFA, CHROMOLITH® ODS S5 4.6×50 mm, gradient=4 min, wavelength=220 nm). Chiral HPLC RT: 8.661 min(AD, 60% (EtOH/MeOH)/heptane)>99% ee. (on AD chiral column desired is the first peak, which is the second peak on the IC SFC).

Workup

  1. customThe desired stereoisomer was collected as the second peak in the elution order
  2. customAfter evaporation of solvent

Sources & evidence

ORD record
ord-b0eabd0cdfe149fdbe8d1d32f17f0cd0
Source dataset
uspto-grants-2015_09
Patent number
US09133139B2

Reaction notes

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