Diethyl Ether → HCID 9859894, compound

HRID 28797Notes

Reaction equation

HRID 28797 reaction equation
[CH2:1]1[CH2:5][O:4][CH2:3][CH2:2]1.[F:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1.C(O[CH2:17][CH3:18])C>>[F:6][C:7]1[CH:12]=[CH:11][C:10]([O:13][C@H:18]2[CH:17]=[CH:5][C:1]3[C:2](=[CH:5][CH:1]=[CH:2][CH:3]=3)[C@@H:3]2[OH:4])=[CH:9][CH:8]=1

Participants

4

Reactant 3

HCID 3283Diethyl EtherHCID 8028TetrahydrofuranHCID 97324-Fluorophenol

Product 1

HCID 9859894HCID 9859894, compoundYield 92%

Conditions

Temperature
80 °C

Procedure

To a flame dried round-bottomed flask, [Rh(COD)Cl]2 (1.7 mg, 0.0035 mmol), (S)—(R)-PPF-PtBu2 (3.8 mg, 0.0069 mmol) and 1 (100 mg, 0.694 mmol) were added followed by addition of THF (2.5 mL) and 4-fluorophenol (389 mg, 3.47 mmol). The mixture was heated at 80° C. for 5 hours, then poured into diethyl ether and extracted 3 times with 10% aqueous sodium hydroxide solution. The aqueous extracts were combined and back-extracted three times with diethyl ether. The combined ether extracts were washed with brine and dried with anhydrous sodium sulfate. The solvents were removed in vacuo, yielding a solid which was purified by flash chromatography on silica gel (10% ethyl acetate in hexanes) giving a white crystalline solid 7 (163 mg, 92%). The ee was determined to be 97% by HPLC analysis on a CHIALCEL OD column, λ=486 nm). Retention times in 1.5% isopropanol in hexanes were 28.1 min (major) and 2, 9.5 min. Rf=0.39 on silica (20% ethyl acetate in hexanes); mp 127-129° C. (Et2O); [α]25D=+216° (c=9.5, CHCl3). IR (KBr, cm−1) 3309 (b), 3071 (w), 2864 (w), 1504 (s), 1284 (m), 1052 (s), 781 (s), 692 (m); 1H NMR (400 MHz, CDCl3): δ 7.63-7.61 (1H, m), 7.31-7.26 (2H, m), 7.12-7.10 (1H, m), 7.00-6.95 (2H, m), 6.92-6.88 (2H, m), 6.51 (1H, dd, J=2.1, 9.9 Hz), 5.98 (1H, dd, J=2.2, 9.9 Hz), 5.15 (1H, dd, J=3.6, 10.0 Hz), 5.01 (1H, ddd, J=2.1, 2.1, 10.1 Hz), 2.54 (1H, d, J=3.8 Hz); 13C NMR (400 MHz, CDCl3): δ 157.6 (d, JC-F=239 Hz), 156.4, 153.4, 135.4, 131.8, 129.1, 128.2, 126.5, 125.7, 125.2, 117.5 (d, JC-F=8 Hz), 116.1 (d, JC-F=23.5 Hz);. HRMS calcd for (M+) (C16H13O2F): 256.0810. Found: 256.0911.

Workup

  1. extractionextracted 3 times with 10% aqueous sodium hydroxide solution
  2. extractionback-extracted three times with diethyl ether
  3. washThe combined ether extracts were washed with brine
  4. dry with materialdried with anhydrous sodium sulfate
  5. customThe solvents were removed in vacuo
  6. customyielding a solid which
  7. customwas purified by flash chromatography on silica gel (10% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-9a3e203cbef749ff862432f37362ef97
Source dataset
uspto-grants-2008_09
Patent number
US07420003B2

Reaction notes

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