Carbon Dioxide → HCID 58551114, compound

HRID 1908191Notes

Reaction equation

HRID 1908191 reaction equation
[O:1]1[CH2:5][CH2:4][CH:3]([S:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]([N:17]3[CH2:22][CH2:21][C:20]4([O:27][C:26]5[CH:28]=[CH:29][CH:30]=[CH:31][C:25]=5[N:24]5[C:32]([C:35]([F:38])([F:37])[F:36])=[CH:33][CH:34]=[C:23]45)[CH2:19][CH2:18]3)=[O:16])=[CH:11][CH:10]=2)(=[O:8])=[O:7])[CH2:2]1.CC(O)C.C(=O)=O>CO>[O:1]1[CH2:5][CH2:4][C@H:3]([S:6]([C:9]2[CH:10]=[CH:11][C:12]([C:15]([N:17]3[CH2:18][CH2:19][C:20]4([C:23]5=[CH:34][CH:33]=[C:32]([C:35]([F:37])([F:36])[F:38])[N:24]5[C:25]5[CH:31]=[CH:30][CH:29]=[CH:28][C:26]=5[O:27]4)[CH2:21][CH2:22]3)=[O:16])=[CH:13][CH:14]=2)(=[O:8])=[O:7])[CH2:2]1

Participants

5

Reactant 3

HCID 280Carbon DioxideHCID 3776IsopropanolHCID 58551378HCID 58551378, compound

Product 1

HCID 58551114HCID 58551114, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(4-(Tetrahydrofuran-3-ylsulfonyl)phenyl)(1-(trifluoromethyl)spiro[benzo[b]pyrrolo[1,2-d][1,4]oxazine-4,4′-piperidine]-1′-yl)methanone was subjected to chiral SFC (column: Phenomenex Lux Cellulose-2 (250×10 mm), 5 μm; mobile phase: 40% IPA w/0.2% DEA, 60% CO2; concentration: 30 mg/mL in MeOH; injection volume: 20 μA; pressure: 100 bar; detection wavelength: 254 nm) to give two peaks. For each enantiomer, the solvent was evaporated and the residue was dissolved in ethyl acetate. The solution was washed with aqueous 1M hydrochloric acid (1×1 mL), a saturated aqueous solution of sodium bicarbonate (1×1 mL) and a saturated aqueous solution of sodium chloride (1×1 mL). The organic layer was dried over sodium sulfate, filtered and the solvent was evaporated under reduced pressure to yield [4-[(3S)-tetrahydrofuran-3-yl]sulfonylphenyl]-[1′-(trifluoromethyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone as a yellow solid (peak 1, the stereochemistry was randomly assigned): ESI-MS m/z calc. 546.1. found 547.2 (M+1)+; Retention time: 1.93 minutes (3 min run); NMR (400 MHz, DMSO) δ 7.99 (d, J=8.4 Hz, 2H), 7.74 (d, J=8.3 Hz, 2H), 7.57 (d, J=8.0 Hz, 1H), 7.37-7.14 (m, 3H), 7.03 (d, J=3.9 Hz, 1H), 6.40 (d, J=4.0 Hz, 1H), 4.53-4.36 (m, 1H), 4.33-4.19 (m, 1H), 4.08-3.94 (m, 1H), 3.91-3.58 (m, 3H), 3.56-3.16 (m, 3H), 2.19-1.82 (m, 6H) and [4[(3R)-tetrahydrofuran-3-yl]sulfonylphenyl]-[1′-(trifluoromethyl)spiro[piperidine-4,4′-pyrrolo[2,1-c][1,4]benzoxazine]-1-yl]methanone as a yellow solid (peak 2, the stereochemistry was randomly assigned): ESI-MS m/z calc. 546.1. found 547.2 (M+1)+; Retention time: 1.93 minutes (3 min run); 1H NMR (400 MHz, DMSO) δ 7.99 (d, J=8.3 Hz, 2H), 7.74 (d, J=8.3 Hz, 2H), 7.57 (d, J=8.2 Hz, 1H), 7.36-7.14 (m, 3H), 7.03 (d, J=3.9 Hz, 1H), 6.40 (d, J=4.0 Hz, 1H), 4.54-4.36 (m, 1H), 4.33-4.17 (m, 1H), 4.09-3.95 (m, 1H), 3.90-3.59 (m, 3H), 3.58-3.12 (m, 3H), 2.24-1.77 (m, 6H).

Workup

  1. customto give two peaks
  2. customFor each enantiomer, the solvent was evaporated
  3. dissolutionthe residue was dissolved in ethyl acetate
  4. washThe solution was washed with aqueous 1M hydrochloric acid (1×1 mL)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent was evaporated under reduced pressure

Sources & evidence

ORD record
ord-80fdae9e51c4463fa21a47274e12b317
Source dataset
uspto-grants-2013_12
Patent number
US08598164B2

Reaction notes

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