Sodium Bicarbonate → (5R)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-5-hydroxymethyloxazolidin-2-one

HRID 723809Notes

Reaction equation

HRID 723809 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([NH:8][C:9](OCC2C=CC=CC=2)=O)[CH:5]=[CH:4][C:3]=1[C:19]1[CH2:20][CH2:21][S:22][CH2:23][CH:24]=1.C([Li])CCC.[C:30]([O:35][CH2:36][C@@H:37]1[O:39]C1)(=[O:34])CCC.C(=O)(O)[O-].[Na+]>O1CCCC1.CO>[S:22]1[CH2:21][CH:20]=[C:19]([C:3]2[CH:4]=[CH:5][C:6]([N:8]3[CH2:9][C@H:36]([CH2:37][OH:39])[O:35][C:30]3=[O:34])=[CH:7][C:2]=2[F:1])[CH2:24][CH2:23]1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 2724536(2R)-Oxiran-2-ylmethyl butanoateHCID 112564024-(2-Fluoro-4-benzyloxycarbonylaminophenyl)-3,6-dihydro-2H-thiopyranHCID 178418339Butyllithium

Product 1

HCID 11335852(5R)-3-[4-(3,6-dihydro-2H-thiopyran-4-yl)-3-fluorophenyl]-5-hydroxymethyloxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

4-(2-Fluoro-4-benzyloxycarbonylaminophenyl)-3,6-dihydro-2H-thiopyran (15.3 g, 44.6 mM) was dissolved in dry tetrahydrofuran (175 ml) and stirred under nitrogen at −70° C. n-Butyllithium (1.6M in hexanes, 30 ml, 175 mM) was run in over 20 minutes, keeping the temperature below −60°, and the mixture then stirred a further 10 minutes at −70° C. A solution of (R)-glycidyl butyrate (6.42 g, 44.62 mM) dissolved in dry tetrahydrofuran (10 ml) was added dropwise over 10 minutes keeping temperature below −60°, and the mixture left to warm to ambient temperature over 18 hours. Methanol (29 ml) was added, and the mixture stirred for 10 minutes only. Saturated aqueous sodium bicarbonate (200 ml) was added, and the mixture extracted with ethyl acetate (400 ml). The extract was washed with saturated aqueous sodium bicarbonate (100 ml), brine (100 ml), dried (magnesium sulfate). Filtered and evaporated. The crude product was purified on a 300 g silica sinter column, eluting with a gradient from 0% to 100% ethyl acetate in dichloromethane. Relevant fractions were combined, reduced to a small volume, and diluted with an excess of isohexane to precipitate the desired product (11.3 g). MS (ESP): 310 (MH+) for C15H16FNO3S

Workup

  1. customwas run in over 20 minutes
  2. customthe temperature below −60°
  3. additionwas added dropwise over 10 minutes
  4. customtemperature below −60°
  5. waitthe mixture left
  6. temperatureto warm to ambient temperature over 18 hours
  7. stirringthe mixture stirred for 10 minutes only
  8. extractionthe mixture extracted with ethyl acetate (400 ml)
  9. washThe extract was washed with saturated aqueous sodium bicarbonate (100 ml), brine (100 ml)
  10. dry with materialdried (magnesium sulfate)
  11. filtrationFiltered
  12. customevaporated
  13. customThe crude product was purified on a 300 g silica sinter column
  14. washeluting with a gradient from 0% to 100% ethyl acetate in dichloromethane
  15. additiondiluted with an excess of isohexane
  16. customto precipitate the desired product (11.3 g)

Sources & evidence

ORD record
ord-b0407fbc9d1a4a62b7cc523411305e23
Source dataset
uspto-grants-2006_11
Patent number
US07141583B2

Reaction notes

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