Sulfuric Acid → HCID 66658338, compound

HRID 2408800Notes

Reaction equation

HRID 2408800 reaction equation
C(OC([C:6]1[C:7](=[O:26])[N:8]([CH2:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=2)[C@@H:9]2[C@H:14]([C:15]=1[OH:16])[C@@H:13]1[CH2:17][C@H:10]2[CH2:11][CH2:12]1)=O)C.S(=O)(=O)(O)O>O1CCOCC1>[F:25][C:22]1[CH:21]=[CH:20][C:19]([CH2:18][N:8]2[C:7](=[O:26])[CH:6]=[C:15]([OH:16])[C@H:14]3[C@@H:9]2[C@H:10]2[CH2:17][C@@H:13]3[CH2:12][CH2:11]2)=[CH:24][CH:23]=1

Participants

4

Reactant 2

HCID 1118Sulfuric AcidHCID 66657981HCID 66657981, compound

Product 1

HCID 66658338HCID 66658338, compoundYield 54%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

(1R,2S,7R,8S)-3-(4-Fluoro-benzyl)-6-hydroxy-4-oxo-3-aza-tricyclo[6.2.1.02,7]undec-5-ene-5-carboxylic acid ethyl ester was suspended in a 1/1 mixture of 1,4-dioxane and 1.0 M aqueous sulfuric acid solution (200 mL). The mixture was heated to 110° C. for 40 min, and then was allowed to cool to 25° C. The cooled mixture was poured into a separatory funnel and was extracted with ethyl acetate (2×150 mL). The combined organic layers were dried over sodium sulfate, filtered and were concentrated in vacuo to afford a white solid. This material was triturated with hexanes and was collected by filtration, washed with hexanes (2×15 mL) and air-dried to afford the desired product, (1R,2S,7R,8S)-3-(4-fluoro-benzyl)-6-hydroxy-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (2.24 g, 7.80 mmol, 54% over three steps), as a white solid. 1H NMR (major tautomer, 400 MHz, CDCl3) δ: 1.11-1.16 (1H, m), 1.20-1.39 (3H, m), 1.57-1.69 (2H, m), 2.53 (1H, d, J=8.4 Hz), 2.63 (1H, bs), 2.73 (1H, bs), 3.39 (1H, d, J=4.1 Hz), 3.51 (1H, d, J=9.5 Hz), 4.29 (1H, d, J=14.9 Hz), 5.20 (1H, d, J=14.9 Hz), 6.98-7.04 (2H, m), 7.19-7.24 (2H, m).

Workup

  1. temperatureto cool to 25° C
  2. additionThe cooled mixture was poured into a separatory funnel
  3. extractionwas extracted with ethyl acetate (2×150 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationwere concentrated in vacuo
  7. customto afford a white solid
  8. customThis material was triturated with hexanes
  9. filtrationwas collected by filtration
  10. washwashed with hexanes (2×15 mL)
  11. customair-dried

Sources & evidence

ORD record
ord-02e7ebec76c64c39895734fa7284f75b
Source dataset
uspto-grants-2014_08
Patent number
US08815847B2

Reaction notes

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