Carbon Dioxide → HCID 178445761, compound

HRID 1802109Notes

Reaction equation

HRID 1802109 reaction equation
[NH2:1][C:2]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([O:16][C@H:17]1[CH2:22][CH2:21][C@H:20]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:19][CH2:18]1)[CH:10]=[CH:9]2)([CH3:5])[CH2:3][OH:4].C(=O)=O>CO>[NH2:1][C@@:2]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[N:12]=[C:11]([O:16][C@H:17]1[CH2:18][CH2:19][C@H:20]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:21][CH2:22]1)[CH:10]=[CH:9]2)([CH3:5])[CH2:3][OH:4]

Participants

4

Reactant 2

HCID 280Carbon DioxideHCID 178464733HCID 178464733, compound

Product 1

HCID 178445761HCID 178445761, compoundYield 36.8%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

SFC separation of the above 2-amino-2-[2-(4-trans-tert-butyl-cyclohexyloxy)-quinolin-6-yl]-propan-1-ol (Example 78) (100 mg, 0.3 mmol) with Whelk-01 (R,R) (3×15cm) 08-10149 in 15% MeOH(0.1% DEA)/CO2, 100 bar, 85 mL/min, 220 nm gave 62 mg of peak 1 (>99% ee) and 12 mg of peak 2 (>99% ee). Peak 1 was subjected to chromatography purification with CH2Cl2/MeOH(20-50%) give (R)-2-amino-2-(2-(trans-4-tert-butylcyclohexyloxy)quinolin-6-yl)propan-1-ol as a foamy solid (39.4 mg). LCMS 1.42 min 357.30 ([M+1], 100%). 1H NMR (400 MHz, MeOD) δ=8.10 (d, J=8.8 Hz, 1H), 7.86 (s, 1H), 7.78 (s, 2H), 6.87 (d, J=8.8 Hz, 1H), 5.20-5.09 (m, 1H), 3.75 (d, J=11.0 Hz, 1H), 3.70 (d, J=11.0 Hz, 1H), 2.29 (d, J=8.0 Hz, 2H), 1.93 (d, J=14.5 Hz, 2H), 1.55 (s, 3H), 1.52-1.38 (m, 2H), 1.38-1.23 (m, 2H), 1.20-1.07 (m, 1H), 0.94 (s, 9H).

Workup

  1. customgave 62 mg of peak 1 (>99% ee) and 12 mg of peak 2 (>99% ee)
  2. customPeak 1 was subjected to chromatography purification with CH2Cl2/MeOH(20-50%)

Sources & evidence

ORD record
ord-20065cc1d2324037b66c48c90ba3b2af
Source dataset
uspto-grants-2013_01
Patent number
US08349849B2

Reaction notes

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