Tetrahydrofuran → HCID 86754235, compound

HRID 618779Notes

Reaction equation

HRID 618779 reaction equation
C1([CH2:7][O:8][C:9]([N:11]2[CH:20]=[CH:19][N:18]3[C:13](=[CH:14][O:15][C:16]4[CH:24]=[C:23]([NH:25][C:26]([O:28]CC5C=CC=CC=5)=[O:27])[CH:22]=[CH:21][C:17]=43)[CH2:12]2)=[O:10])C=CC=CC=1.[CH2:36]([Li])[CH2:37][CH2:38][CH3:39].[C:41](OC[C@@H]1OC1)(=[O:45])[CH2:42][CH2:43]C.O1CC[CH2:53][CH2:52]1>>[C:36]1([CH2:7][O:8][C:9]([N:11]2[CH2:20][CH2:19][N:18]3[CH:13]([CH2:14][O:15][C:16]4[CH:24]=[C:23]([N:25]5[CH2:43][C@H:42]([CH2:41][OH:45])[O:28][C:26]5=[O:27])[CH:22]=[CH:21][C:17]=43)[CH2:12]2)=[O:10])[CH:53]=[CH:52][CH:39]=[CH:38][CH:37]=1

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 69916010HCID 69916010, compoundHCID 178418339Butyllithium

Product 1

HCID 86754235HCID 86754235, compound

Conditions

Temperature
-78 °C

Procedure

To a flame dried flask under an inert atmosphere containing 8-[[(phenylmethoxy)carbonyl]amino]-pyrazino[2,1-c][1,4]benzoxazine-3(4H)-carboxylic acid phenylmethyl ester (Step 7, 1.00 g, 2.11 mmol) in tetrahydrofuran (20 mL) cooled to -78° C. is added n-butyl lithium (1.6M in hexanes) (1.39 mL, 2.22 mmol) followed by (R)-glycidyl butyrate (0.33 mL, 2.32 mmol). The reaction is stirred 15 hours and quenched with saturated ammonium chloride (20 mL). The aqueous phase is separated and extracted with ethyl acetate (2×20 mL). The organics are combined, washed with saline, dried over Na2SO4, concentrated in vacuo, and chromatographed on silica gel (230-400 mesh, 200 mL), eluting with chloroform/methanol (99/1). The appropriate fractions are combined (Rf =0.16, TLC, chloroform/methanol, 95/5) and concentrated in vacuo to give the title compound, NMR (CDCl3) 7.39-7.31, 7.04, 6.96, 6.75, 5.16, 4.68, 4.20-3.99, 4.15, 3.96-3.86, 3.73-3.62, 3.16-2.97, 2.82-2.66.

Workup

  1. customTo a flame dried flask under an inert atmosphere
  2. customquenched with saturated ammonium chloride (20 mL)
  3. customThe aqueous phase is separated
  4. extractionextracted with ethyl acetate (2×20 mL)
  5. washwashed with saline
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated in vacuo
  8. customchromatographed on silica gel (230-400 mesh, 200 mL)
  9. washeluting with chloroform/methanol (99/1)
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6c11592c12bf4871b8c0be97bae467f6
Source dataset
uspto-grants-1999_09
Patent number
US05955460

Reaction notes

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