Methanol → HCID 15887508, compound

HRID 1004834Notes

Reaction equation

HRID 1004834 reaction equation
CC(OC([N:8]1[CH2:13][CH2:12][CH:11]=[C:10]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:24][C@H:23]([CH2:25][NH:26][C:27](=[O:29])[CH3:28])[O:22][C:21]3=[O:30])=[CH:16][C:15]=2[F:31])[CH2:9]1)=O)(C)C.I[Si](C)(C)C.CO.[C:39]([O:42][CH2:43][C:44](Cl)=[O:45])(=[O:41])[CH3:40]>C(#N)C.C(Cl)Cl.C(N(CC)CC)C>[O:30]=[C:21]1[N:20]([C:17]2[CH:18]=[CH:19][C:14]([C:10]3[CH2:9][N:8]([C:44](=[O:45])[CH2:43][O:42][C:39](=[O:41])[CH3:40])[CH2:13][CH2:12][CH:11]=3)=[C:15]([F:31])[CH:16]=2)[CH2:24][C@H:23]([CH2:25][NH:26][C:27](=[O:29])[CH3:28])[O:22]1

Participants

8

Reactant 4

HCID 887MethanolHCID 26297Acetoxyacetyl chlorideHCID 85247Trimethylsilyl iodide2×HCID 53774727HCID 53774727, compound

Product 1

HCID 15887508HCID 15887508, compound

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

A solution of (S)-3-[4-[5-[(acetylamino)methyl]-2-oxo-3-oxazolidinyl]-2-fluorophenyl]-5,6-dihydro-1(2H)-pyridinecarboxylic acid 1,1-dimethylethyl ester (EXAMPLE 70, Step 2, 158 mg) in dry acetonitrile under N2 is treated with iodotrimethylsilane (62 μL) dropwise, and the resulting solution is stirred at ambient temperature for 50 mins, during which additional iodotrimethylsilane (25 μL) is added. The reaction is then treated with methanol (59 μL), stirred for 5 mins and concentrated under reduced pressure to give the deprotected intermediate. A mixture of this intermediate and triethylamine (0.122 mL) in dry methylene chloride (3.6 mL) at 0° C. under N2 is treated with acetoxyacetyl chloride (47 μL), and the resulting mixture is stirred at 0° C. for 2 hrs and at ambient temperature for 2 hrs and then diluted with methylene chloride (20 mL), washed with water (10 mL), saturated aqueous sodium bicarbonate (10 mL) and saline (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue is chromatographed on silica gel (70-230 mesh, 15 g), eluting with methanol/methylene chloride (5/95), and those fractions with an Rf =0.5 by TLC (methanol/chloroform, 10/90) are pooled and concentrated to give the title compound, HRMS calculated for C21H24N3F1O6 +H1 : 434.1727. Found: 434.1741.

Workup

  1. additionis added
  2. concentrationconcentrated under reduced pressure
  3. customto give the deprotected intermediate
  4. stirringthe resulting mixture is stirred at 0° C. for 2 hrs and at ambient temperature for 2 hrs
  5. washwashed with water (10 mL), saturated aqueous sodium bicarbonate (10 mL) and saline (10 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue is chromatographed on silica gel (70-230 mesh, 15 g)
  9. washeluting with methanol/methylene chloride (5/95)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-0ecb69a68afe4cf9933a1ffd28ff65d4
Source dataset
uspto-grants-2000_04
Patent number
US06051716

Reaction notes

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