Acetic Acid → HCID 131726781, compound

HRID 2057158Notes

Reaction equation

HRID 2057158 reaction equation
[C:1]([N:4]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C@H:5]([C:10]([OH:12])=[O:11])[C@@H:6]([CH2:8][F:9])[OH:7])([OH:3])=[O:2].[Si:21](Cl)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22].N1C=CN=C1.C(O)(=O)C>CN(C=O)C.ClCCl.C1COCC1.CO>[C:1]([N:4]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C@H:5]([C:10]([OH:12])=[O:11])[C@@H:6]([CH2:8][F:9])[O:7][Si:21]([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:23])[CH3:22])([OH:3])=[O:2]

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chlorideHCID 86589109HCID 86589109, compound

Product 1

HCID 131726781HCID 131726781, compoundYield 86%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 21899815MeOH tetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of N-carboxybenzyloxy-(2S,3S)-4-fluorothreonine 102 (0.060 g, 0.22 mmol) in DMF (3 ml) was added tert-butyldimethylsilyl chloride (0.073 g, 0.49 mmol) and imidazole (0.033 g, 0.49 mmol). The solution was gently heated at 80° C. for 18 hours. After allowing the solution to cool to room temperature, the solution was diluted with dichloromethane (15 ml) and washed with 1N HCl solution (3×10 ml). The organic layer was dried (MgSO4) and the solvent was removed in vacuo to give a yellow oil. The residue was redissolved in a 1:1 THF/methanol solution (4 ml) and upon stirring 50% aqueous acetic acid (2 ml) was added. After stirring the solution vigorously for 4 hours the solvent was removed in vacuo to give a yellow oil. Trace amounts of acetic acid were removed by treatment of the residue in ethyl acetate (5 ml) with saturated sodium hydrogen carbonate solution (10 ml). The organic layer was dried (MgSO4) and the solvent removed in vacuo to afford N-carboxybenzyloxy-O-tert-butyldimethylsilyl-(2S,3S)-4-fluorothreonine 103 as a pale yellow oil (0.073 g, 86% yield); 1H (400 MHz, CDCl3) 9.50 (1H, bs, OH, exchange with CH3OD), 7.60-7.20 (5H, m, Ph), 6.25, 5.75 and 5.45 (1H, 3×d, J 9.1, NH, exchange with CH3OD), 5.20-5.10 (2H, m, CH2Ph), 4.75-4.20 (4H, H-2, H-3, 4-CH2), 1.00-0.80 (9H, 2×s, SiC(CH3)3), 0.15-0.00 (6H, m, Si(CH3)2); 19F (376 MHz, CDCl3) −224.82 and −225.39 (2×dtJ 47, 4 due to rotamers).

Workup

  1. temperatureto cool to room temperature
  2. washwashed with 1N HCl solution (3×10 ml)
  3. dry with materialThe organic layer was dried (MgSO4)
  4. customthe solvent was removed in vacuo
  5. customto give a yellow oil
  6. additionwas added
  7. customwas removed in vacuo
  8. customto give a yellow oil
  9. customTrace amounts of acetic acid were removed by treatment of the residue in ethyl acetate (5 ml) with saturated sodium hydrogen carbonate solution (10 ml)
  10. dry with materialThe organic layer was dried (MgSO4)
  11. customthe solvent removed in vacuo

Sources & evidence

ORD record
ord-3f1e7a71d41c440d9f578f00a15d3eee
Source dataset
uspto-grants-2008_02
Patent number
US07335792B2

Reaction notes

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