Tetrahydrofuran → HCID 68000480, compound

HRID 932169Notes

Reaction equation

HRID 932169 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@H:21]([CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][O:25]3)[CH2:22][CH3:23])[C:11](=[O:30])[C@:10]([CH2:32][CH:33]=[O:34])([CH3:31])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[OH:35]P([O-])(O)=O.[K+].C1COCC1.Cl([O-])=O.[Na+]>O.C(O)(C)(C)C.CC(=CC)C>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@H:21]([CH:24]3[CH2:29][CH2:28][CH2:27][CH2:26][O:25]3)[CH2:22][CH3:23])[C:11](=[O:30])[C@:10]([CH2:32][C:33]([OH:35])=[O:34])([CH3:31])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 516951Monobasic potassium phosphateHCID 23668197Sodium ChloriteHCID 86660734HCID 86660734, compound

Product 1

HCID 68000480HCID 68000480, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6386tert-ButanolSolventHCID 105532-Methyl-2-buteneSolvent

Procedure

A solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((1S)-1-(tetrahydro-2H-pyran-2-yl)propyl)piperidin-3-yl)acetaldehyde (3 mg, 5.97 μmoL; mixture of stereoisomers, Example 224, Step E) in a solution of 1.25 M potassium phosphate monobasic in water (0.050 mL), t-butanol (0.050 mL) and 2.0 M 2-methylbut-2-ene in THF (0.15 mL, 0.30 mmol) was treated with sodium chlorite (2.16 mg, 0.024 mmol) at ambient temperature for 3 h. The reaction was quenched with 1 M sodium thiosulphate solution (0.03 mL). After 10 min, the mixture was acidified with 1M potassium bisulphate solution (0.03 mL) and extracted with ethyl acetate. The organic layers were washed with sat. aq. NaCl solution and dried over anhydrous sodium sulfate. Purification by reversed phase preparatory HPLC (eluent: 0 to 100% MeCN +0.1% TFA in water +0.1% TFA, over 20 minutes) gave the title compound as the first eluting isomer.

Workup

  1. customThe reaction was quenched with 1 M sodium thiosulphate solution (0.03 mL)
  2. extractionextracted with ethyl acetate
  3. washThe organic layers were washed with sat. aq. NaCl solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. customPurification by reversed phase preparatory HPLC (eluent: 0 to 100% MeCN +0.1% TFA in water +0.1% TFA, over 20 minutes)

Sources & evidence

ORD record
ord-8c8eab37a8534a979025b8cf52662aa6
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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