Tetrahydrofuran → Snap-7915

HRID 2269216Notes

Reaction equation

HRID 2269216 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C@H:13]([CH3:14])[O:12][C:11](=[O:15])[NH:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[Li]CCCC.[F:21][C:22]1[CH:27]=[CH:26][C:25]([CH:28]2[CH2:33][CH2:32][N:31]([CH2:34][CH2:35][CH2:36][NH2:37])[CH2:30][CH2:29]2)=[CH:24][CH:23]=1.C1C[O:41][CH2:40]C1>ClC(OC1C=CC([N+]([O-])=O)=CC=1)=O.O>[F:1][C:2]1[CH:3]=[C:4]([C@H:9]2[C@H:13]([CH3:14])[O:12][C:11](=[O:15])[N:10]2[C:40]([NH:37][CH2:36][CH2:35][CH2:34][N:31]2[CH2:32][CH2:33][CH:28]([C:25]3[CH:26]=[CH:27][C:22]([F:21])=[CH:23][CH:24]=3)[CH2:29][CH2:30]2)=[O:41])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 8028Tetrahydrofuran3×HCID 101985993-(4-(4-Fluorophenyl)piperidin-1-yl)propan-1-amineHCID 105127504(S)-(3,4-difluorophenyl)-5(S)-methyloxazolidin-2-oneHCID 178418339Butyllithium2×

Product 1

HCID 9830741Snap-7915

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 821294-Nitrophenyl chloroformateSolvent2×

Conditions

Temperature
-60 °C

Procedure

4(S)-(3,4-difluorophenyl)-5(S)-methyloxazolidin-2-one (2 g, 9.4 mmole) was dissolved in THF (20 ml) and cooled to −60° C. for the dropwise addition of n-BuLi (4 ml, 2.5 M in hexane). In a separate flask, p-nitrophenyl chloroformate was dissolved in 20 ml THF and cooled to −60° C. When the addition of n-BuLi was complete, the mixture was aged at −60° C. for 30 minutes. and then transferred via cannula to the p-nitrophenyl chloroformate solution. The reaction mixture was then allowed to warm to room temperature, and reaction progress was monitored by HPLC. After 2.5 hours, 3-(4-(4-fluorophenyl)piperidin-1-yl)propylamine (Example 1) (2.2 g, 9.4 mmole) in THF was added. After 3.5 hours at room temperature age, the solution was diluted with 100 ml water and extracted with 2×50 ml MTBE. The MTBE extractions were combined and washed with 2×50 ml 1M sulfuric acid. The aqueous washes were combined, rendered basic (pH=9-10) with 2 M sodium carbonate, and extracted with 2×100 ml MTBE. The MTBE layers were combined and concentrated, and the title compound was isolated by column chromatography on silica gel using 9:1 EtOAc:MeOH.

Workup

  1. temperatureto warm to room temperature
  2. customreaction progress
  3. waitAfter 2.5 hours
  4. waitAfter 3.5 hours at room temperature age
  5. extractionextracted with 2×50 ml MTBE
  6. extractionThe MTBE extractions
  7. washwashed with 2×50 ml 1M sulfuric acid
  8. extractionextracted with 2×100 ml MTBE
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-d5d5553bba6e44a8a5394252f7aa7941
Source dataset
uspto-grants-2001_12
Patent number
US06329393B1

Reaction notes

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