Tetrahydrofuran → HCID 90424169, compound

HRID 1055169Notes

Reaction equation

HRID 1055169 reaction equation
[Si:1]([O:18][CH2:19][C@H:20](O)[CH2:21][N:22]1[CH:26]=[CH:25][N:24]=[C:23]1[CH2:27][OH:28])([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O1CCCC1.[H-].[Na+].C(=O)(O)[O-].[Na+]>ClCCl>[C:14]([Si:1]([O:18][CH2:19][C@@H:20]1[O:28][CH2:27][C:23]2=[N:24][CH:25]=[CH:26][N:22]2[CH2:21]1)([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([CH3:17])([CH3:15])[CH3:16]

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 90424018HCID 90424018, compound2×

Product 1

HCID 90424169HCID 90424169, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

Separately, prepare a −78° C. solution of (2R)-1-[tert-butyl(diphenyl)silyl]oxy-3-[2-(hydroxymethyl)imidazol-1-yl]propan-2-ol (5.3 g; 1.0 equiv; 12.91 mmoles) in dichloromethane (25 mL). Add the in situ prepared iodinating reagent dropwise to the solution of (2R)-1-[tert-butyl(diphenyl)silyl]oxy-3-[2-(hydroxymethyl)imidazol-1-yl]propan-2-ol, with the orange color quickly fading to nearly colorless. Maintain the solution at −78° C. for 30 minutes, then allow it to warm to 0° C. and maintain for 10 minutes. Re-cool the solution to −78° C., and add tetrahydrofuran (100 mL) followed by 60% sodium hydride (1.14 g; 2.2 equiv; 28.40 mmoles). Slowly warm the solution to 0° C. over 30 minutes, and then to ambient temperature for 1 hour. Pour the mixture slowly into 50% saturated sodium bicarbonate solution and extract with dichloromethane (4×100 mL). Dry the combined organic extracts over magnesium sulfate, filter, and concentrate. Purify the crude product by column chromatography (10 to 100% ethyl acetate in hexanes) to afford the desired product contaminated with triphenylphosphine oxide. Further purify by SCX ion-exchange chromatography (10% methanol in dichloromethane to 10% (4N ammonia in methanol) in dichloromethane) to afford the desired tert-butyl-[[(6R)-6,8-dihydro-5H-imidazo[2,1-c][1,4]oxazin-6-yl]methoxy]-diphenyl-silane (1.86 g; 37%). MS (m/z): 393(M+1).

Workup

  1. additionAdd the in situ
  2. customprepared
  3. temperatureto warm to 0° C.
  4. temperaturemaintain for 10 minutes
  5. temperatureSlowly warm the solution to 0° C. over 30 minutes
  6. extractionextract with dichloromethane (4×100 mL)
  7. dry with materialDry the combined organic extracts over magnesium sulfate
  8. filtrationfilter
  9. concentrationconcentrate
  10. customPurify the crude product by column chromatography (10 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-3cb5e7f13c1144b2881364a92de485a9
Source dataset
uspto-grants-2016_07
Patent number
US09394317B2

Reaction notes

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