Cerium trichloride → [trans-8-Hydroxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methoxy-phenyl)methanone

HRID 1478431Notes

Reaction equation

HRID 1478431 reaction equation
[CH:1]([O:4][C:5]1[CH:30]=[CH:29][C:8]([C:9]([N:11]2[CH2:16][CH2:15][C:14]3([O:21][CH:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH2:19][C:18](=[O:28])[CH2:17]3)[CH2:13][CH2:12]2)=[O:10])=[CH:7][C:6]=1[O:31][CH3:32])([CH3:3])[CH3:2].Cl[Ce](Cl)Cl.[BH4-].[Na+]>CO>[OH:28][C@H:18]1[CH2:19][C@@H:20]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[O:21][C:14]2([CH2:15][CH2:16][N:11]([C:9]([C:8]3[CH:29]=[CH:30][C:5]([O:4][CH:1]([CH3:2])[CH3:3])=[C:6]([O:31][CH3:32])[CH:7]=3)=[O:10])[CH2:12][CH2:13]2)[CH2:17]1.[OH:28][C@H:18]1[CH2:19][C@H:20]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[O:21][C:14]2([CH2:15][CH2:16][N:11]([C:9]([C:8]3[CH:29]=[CH:30][C:5]([O:4][CH:1]([CH3:2])[CH3:3])=[C:6]([O:31][CH3:32])[CH:7]=3)=[O:10])[CH2:12][CH2:13]2)[CH2:17]1

Participants

6

Reactant 3

HCID 161282Cerium trichlorideHCID 4311764Sodium borohydrideHCID 897085363-(4-Isopropoxy-3-methoxy-benzoyl)-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-8-one

Product 2

HCID 117772865[trans-8-Hydroxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methoxy-phenyl)methanoneHCID 117772949[cis-8-Hydroxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methoxy-phenyl)methanone

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-(4-isopropoxy-3-methoxy-benzoyl)-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-8-one (4.50 g, 10.3 mmol) in MeOH (110 mL) was added trichlorocerium (2.79 g, 11.3 mmol). The mixture was stirred at room temperature for 5 minutes. Sodium borohydride (467 mg, 12.4 mmol) was added. The mixture was stirred at room temperature for 20 minutes. The reaction was quenched with water and extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated to dryness. The crude material was purified by column chromatography (40-60% ethyl acetate-Hex) to provide [cis-8-hydroxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methoxy-phenyl)methanone (1.5 g) and [trans-8-hydroxy-10-phenyl-11-oxa-3-azaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methoxy-phenyl)methanone (1.3 g). cis-isomer: 1H NMR (400 MHz, CDCl3) δ 7.43-7.33 (m, 4H), 7.33-7.27 (m, 1H), 6.96 (d, J=1.6 Hz, 1H), 6.95-6.90 (m, 1H), 6.86 (d, J=8.2 Hz, 1H), 4.65-4.48 (m, 2H), 4.23-4.05 (m, 2H), 3.95-3.75 (m, 1H), 3.85 (s, 3H), 3.49 (s, 1H), 3.20 (s, 1H), 2.25 (dd, J=20.6, 8.4 Hz, 2H), 1.98 (dd, J=12.5, 2.9 Hz, 1H), 1.73 (s, 2H), 1.62-1.40 (m, 3H), 1.37 (t, J=6.0 Hz, 6H). ESI-MS m/z calc. 439.24, found 440.4 (M+1)+; Retention time: 1.49 minutes (3 minute run). trans-isomer 1H NMR (400 MHz, CDCl3) δ 7.43-7.38 (m, 2H), 7.39-7.33 (m, 2H), 7.31-7.24 (m, 1H), 6.96 (d, J=1.7 Hz, 1H), 6.92 (dd, J=8.2, 1.8 Hz, 1H), 6.85 (d, J=8.2 Hz, 1H), 4.97 (d, J=11.2 Hz, 1H), 4.55 (dt, J=12.2, 6.1 Hz, 1H), 4.44-4.32 (m, 1H), 4.05-3.75 (m, 2H), 3.85 (s, 3H), 3.49 (s, 1H), 3.24 (s, 1H), 2.77 (dd, J=25.2, 13.7 Hz, 1H), 1.96 (d, J=13.4 Hz, 1H), 1.84-1.70 (m, 2H), 1.70-1.54 (m, 5H), 1.37 (d, J=6.1 Hz, 6H). ESI-MS m/z calc. 439.24, found 440.2 (M+1)+; Retention time: 1.61 minutes (3 minute run).

Workup

  1. stirringThe mixture was stirred at room temperature for 20 minutes
  2. customThe reaction was quenched with water
  3. extractionextracted with ethyl acetate (2×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe crude material was purified by column chromatography (40-60% ethyl acetate-Hex)

Sources & evidence

ORD record
ord-0853217514e24b4283de12cbc155f63f
Source dataset
uspto-grants-2016_08
Patent number
US09403839B2

Reaction notes

Loading…