Triethylamine → HCID 131720947, compound

HRID 356729Notes

Reaction equation

HRID 356729 reaction equation
Cl.[F:2][C:3]1[CH:4]=[C:5]([N:15]2[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]2=[O:25])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(N(CC)CC)C.C([O:36][CH2:37][C:38](Cl)=[O:39])(=[O:35])C.C([O:44][CH2:45][C:46](N)=[O:47])(=[O:43])C>O1CCCC1>[OH2:17].[F:2][C:3]1[CH:4]=[C:5]([N:15]2[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]2=[O:25])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][N:12]([C:37](=[O:36])[CH2:38][OH:39])[CH2:11][CH2:10]1.[OH2:35].[OH2:43].[F:2][C:3]1[CH:4]=[C:5]([N:15]2[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]2=[O:25])[CH:6]=[CH:7][C:8]=1[N:9]1[CH2:14][CH2:13][N:12]([C:45](=[O:44])[CH2:46][OH:47])[CH2:11][CH2:10]1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 26297Acetoxyacetyl chlorideHCID 14289617HCID 14289617, compoundHCID 18666949HCID 18666949, compound

Product 1

HCID 131720947HCID 131720947, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred mixture of (S)-N-[[3-[3-fluoro-4(-1-piperazinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide hydrochloride (EXAMPLE 7, 16.2 kg, 43.5 moles), tetrahydrofuran (205 kg) and triethylamine (10.1 kg, 100 moles) is added acetoxyacetyl chloride (6.5 kg, 47.8 moles) in tetrahydrofuran (11.1 kg) over 35 minutes keeping the temperature at 22°-23°. After 40 minutes, at which time TLC and HPLC analysis indicated complete formation of the acetoxyacetamide intermediate, the mixture is concentrated under reduced pressure to 30 l, diluted with methanol (100 l) and concentrated to 30 l. To the residue is added methanol (25 l) and an aqueous solution of potassium carbonate (5.6 kg in 56 l). The resulting mixture is stirred 20 hr at 22°-25° at which time TLC and HPLC analysis indicates the reaction is complete. The pH is adjusted to 7-7.5 with hydrochloric acid (4N, 14.3 l). The mixture is stirred 18 hr at 15°-22° then 3 hrs at 2°-5°. The solids are collected on a filter, washed with water (68 l) and dried at 20°-25° with recycled nitrogen to give the desired product. The crude product is dissolved in water (225 l) at 60°-70°, clarified through a 0.6 micron filter, diluted with water rinse (55 l) and stirred 17 hrs. at 15°. The solids are collected on a filter, washed with water at 15° and dried at 45° with recycled nitrogen to a water content of 0.33%. These solids are dissolved in a solution of ethyl acetate (143 l), methanol (65 l) and water (1.95 l) at 60°-65°. The solution is cooled to 15°-25° and stirred 16 hrs for crystallization. The solids are collected on a filter, washed with ethyl acetate (75 l) and dried with 45° nitrogen to give the desired product. The product is recrystallized two more times from water (147 1 then 133 l) at 60°-70°, clarified each time through a 0.6 micron filter and rinsed with water (40 1 and 30 l). The solids are dried on the filter at 30° with recycled nitrogen to give, after deagglomeration through a mill, the title compound as the sesquihydrate (6.45% water), TLC (silica gel; methanol/methylene chloride, 5/95) Rf =0.45; [α]D =-20° (c=1.0, ethanol).

Workup

  1. customat 22°-23°
  2. concentrationthe mixture is concentrated under reduced pressure to 30 l
  3. additiondiluted with methanol (100 l)
  4. concentrationconcentrated to 30 l
  5. additionTo the residue is added methanol (25 l)
  6. stirringThe mixture is stirred 18 hr at 15°-22°
  7. custom3 hrs
  8. customat 2°-5°
  9. customThe solids are collected on a filter
  10. washwashed with water (68 l)
  11. customdried at 20°-25° with recycled nitrogen

Sources & evidence

ORD record
ord-bc531b4d744a4ecf86042c9689e65e29
Source dataset
uspto-grants-1998_11
Patent number
US05837870

Reaction notes

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