Potassium Carbonate → HCID 67191221, compound

HRID 2355506Notes

Reaction equation

HRID 2355506 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([NH:24][C@@H:25]([CH2:38][CH:39]3[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]3)[CH2:26][N:27]([CH3:37])[C:28]([O:30][CH2:31][CH2:32][Si:33]([CH3:36])([CH3:35])[CH3:34])=[O:29])=[O:23])[CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][O:13]C)[CH:5]=[CH:6][CH:7]=1.[Al+3].[Cl-].[Cl-].[Cl-].C(ON1C(=O)CCC1=O)(OCC[Si](C)(C)C)=O.C([O-])([O-])=O.[K+].[K+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[I-].[Cl-].[Na+].O.C(Cl)Cl.O.CC#N>[Cl:1][C:2]1[CH:3]=[C:4]([C@:8]([C@@H:16]2[CH2:21][CH2:20][CH2:19][N:18]([C:22]([NH:24][C@@H:25]([CH2:38][CH:39]3[CH2:44][CH2:43][CH2:42][CH2:41][CH2:40]3)[CH2:26][N:27]([CH3:37])[C:28]([O:30][CH2:31][CH2:32][Si:33]([CH3:34])([CH3:35])[CH3:36])=[O:29])=[O:23])[CH2:17]2)([OH:15])[CH2:9][CH2:10][CH2:11][CH2:12][OH:13])[CH:5]=[CH:6][CH:7]=1

Participants

10

Reactant 4

HCID 11430Potassium CarbonateHCID 50183862,5-Dioxopyrrolidin-1-yl 2-(trimethylsilyl)ethyl carbonateHCID 6451240Aluminum(III) ChlorideHCID 67192118HCID 67192118, compound

Product 1

HCID 67191221HCID 67191221, compoundYield 25.5%

Reagents, catalysts & solvents 5

HCID 67553Tetrabutylammonium IodideCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

A 100 mL round-bottom flask was charged with of (3R)-3-((S)-1-(3-chlorophenyl)-1-hydroxy-5-methoxypentyl)-N—((S)-3-cyclohexyl-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)-amino)propan-2-yl)piperidine-1-carboxamide (0.6557 g, 1.0 mmol, 1.0 equiv), n-Bu4NI (3.765 g, 10 mmol, 10 equiv), and CH3CN (15 mL). To the flask was added AlCl3 (1.345 g, 10 mmol, 10 equiv) at 0° C. After 4 h, the reaction mixture was quenched with 10% aq Na2CO3 (18 mL) and 1 N aq NaOH (10 mL) and extracted with CH2Cl2 (3×). The combine organic extracts were dried over Na2SO4 and the solvent was removed in vacuo. The crude product was treated with Teoc-OSu (0.534 g, 2.06 mmol), K2CO3 (4.080 g, 29.5 mmol), water (5 mL) and CH2Cl2 (50 mL) at rt for 2.5 h. The mixture was diluted with brine, extracted with CH2Cl2 and dried over Na2SO4. After the solvent was removed in vacuo, the crude product was purified by prep HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 70%→90% CH3CN/H2O, 0.1% CF3COOH over 8 min and then 90% CH3CN/H2O, 0.1% CF3COOH over 10 min, flow rate 25 mL/min) to give (3R)-3-((S)-1-(3-chlorophenyl)-1,5-dihydroxypentyl)-N—((S)-3-cyclohexyl-1-(N-methyl-N-(2-(trimethylsilyl)ethoxycarbonyl)amino)propan-2-yl)piperidine-1-carboxamide (0.1625 g). LC-MS (3 min) tR=2.29 min, m/z 660, 662 (MNa+), 638, 640 (MH+).

Workup

  1. customthe reaction mixture was quenched with 10% aq Na2CO3 (18 mL) and 1 N aq NaOH (10 mL)
  2. extractionextracted with CH2Cl2 (3×)
  3. dry with materialThe combine organic extracts were dried over Na2SO4
  4. customthe solvent was removed in vacuo
  5. extractionextracted with CH2Cl2
  6. dry with materialdried over Na2SO4
  7. customAfter the solvent was removed in vacuo
  8. customthe crude product was purified by prep HPLC (Phenomenex® Luna 5μ C18(2) 100 A, 250×21.20 mm, 5 micron, 70%
  9. customover 8 min
  10. wait90% CH3CN/H2O, 0.1% CF3COOH over 10 min

Sources & evidence

ORD record
ord-7487241b75a34c1fb6065ef1dcd080f9
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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