Pentane → HCID 86268842, compound

HRID 1746637Notes

Reaction equation

HRID 1746637 reaction equation
[C:1]([Si:5]([O:18][C@@H:19]1[C@H:26]2[C@H:22]([O:23][C:24]([CH3:28])([CH3:27])[O:25]2)[C:21]([CH2:29][O:30][C:31]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[C:20]1I)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2].C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:61])(=O)=O)=CC=1.CCCCC.[Li]CCCC>C1COCC1.CCOCC>[C:1]([Si:5]([O:18][C@@H:19]1[C@H:26]2[C@H:22]([O:23][C:24]([CH3:28])([CH3:27])[O:25]2)[C:21]([CH2:29][O:30][C:31]([C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)([C:38]2[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=2)[C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[C:20]1[F:61])([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 8003PentaneHCID 588007N-FluorobenzenesulfonimideHCID 90412667HCID 90412667, compoundHCID 178418339Butyllithium

Product 1

HCID 86268842HCID 86268842, compoundYield 332.8%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

Compound 8 (0.48 kg) and NFSI (N-fluorobenzenesulfonimide) (0.29 kg) was dissolved in THF (3 L) and ether (1 L). To the solution was added 1.5 L of n-pentane, and the mixture was cooled to −78° C. in a dry-ice bath. A solution of n-BuLi in THF (2.5 M, 0.72 L) was added drop wise to the reaction mixture within 4 hours, while keeping the reaction temperature below −70° C. The reaction mixture was stirred another hour until HPLC indicated complete consumption of compound 8. Saturated ammonium chloride solution (aqueous, 2 L) was added drop wise to the reaction mixture. It was then allowed to warm to ambient temperature. Eight such reactions were combined and diluted with 30 L of ethyl acetate. The mixture was stirred for 30 minutes, then the organic phase separated and the aqueous layer was extracted with 20 L of ethyl acetate. The combined organic phase was washed with brine (10 L), dried over sodium sulfate, and concentrated to dryness. HPLC indicated ratio of compound 9 to its corresponding de-fluoro side product was about 3/1. The residue was loaded on a silica gel column (300˜400 mesh) and eluted with petroleum ether/dichloromethane/ethyl acetate (first 100/0/0, then 200/10/1 to remove the front impurities, then changed to 200/15/1 to collect the desired product 9, (then 200/20/1 to collect the side product). Altogether 1.38 kg of compound 9 (yield 36%, purity˜95%) was obtained. 1H-NMR (300 MHz, CDCl3) δ 7.25-7.92 (m, 25H), 5.04 (t, J=7.2 Hz, 1H), 4.45 (m, 1H), 4.33 (m, 1H), 3.98 (d, J=12.0 Hz, 1H), 3.86 (d, J=12.0 Hz, 1H), 1.55 (s, 3H), 1.48 (s, 3H), 1.18 (s, 9H); 13C-NMR DEPT-135 (75 MHz, CDCl3, δ<100) δ 78.70, 75.35, 71.10, 56.39, 28.04, 27.25, 26.82.

Workup

  1. customthe reaction temperature below −70° C
  2. customconsumption of compound 8
  3. additionSaturated ammonium chloride solution (aqueous, 2 L) was added drop wise to the reaction mixture
  4. temperatureto warm to ambient temperature
  5. additiondiluted with 30 L of ethyl acetate
  6. stirringThe mixture was stirred for 30 minutes
  7. customthe organic phase separated
  8. extractionthe aqueous layer was extracted with 20 L of ethyl acetate
  9. washThe combined organic phase was washed with brine (10 L)
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated to dryness
  12. washeluted with petroleum ether/dichloromethane/ethyl acetate (first 100/0/0
  13. custom200/10/1 to remove the front impurities
  14. customto collect the desired product 9
  15. custom(then 200/20/1 to collect the side product)

Sources & evidence

ORD record
ord-6afc5988c307440285e45d85df8e1be9
Source dataset
uspto-grants-2015_10
Patent number
US09150520B2

Reaction notes

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