Tetrahydrofuran → (1S,2S)-6,7-Difluoro-2-methoxy-1,2-dihydro-naphthalen-1-ol

HRID 28790Notes

Reaction equation

HRID 28790 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[CH:8]1[O:13][CH:5]2[CH:6]=[CH:7]1.C1C[O:17][CH2:16]C1>CO>[F:12][C:11]1[CH:10]=[C:9]2[C:4](=[CH:3][C:2]=1[F:1])[C@H:5]([OH:13])[C@@H:6]([O:17][CH3:16])[CH:7]=[CH:8]2

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 120370736,7-Difluoro-1,4-epoxy-1,4-dihydronaphthalene

Product 1

HCID 10198229(1S,2S)-6,7-Difluoro-2-methoxy-1,2-dihydro-naphthalen-1-olYield 88%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a flame dried round bottom flask, [Rh(COD)Cl]2 (2.5 mg, 0.005 mmol), (S)—(R)-PPF-PtBu2 (5.4 mg, 0.010 mmol) and 24 (72 mg, 0.40 mmol) were added followed by addition of THF (1.0 mL) and methanol (1.0 mL). The mixture was heated to reflux for 1 hour. The solvents were then removed in vacuo. The resulting solid was purified by flash chromatography (20% ethyl acetate in hexanes) to give 27 as a white crystalline solid (74.9 mg, 88%). The ee was determined to be 96.4% using HPLC analysis on a CHIRALCEL OD column, λ=486 nm. Retention times in 4% isopropanol in hexanes were 8.9 min and 10.1 min (major). Rf=0.27 on silica gel (30% ethyl acetate:hexanes); mp 129-131° (Et2O); [α]25D=+134.4° (c=9.3, CHCl3); IR (KBr, cm−1) 3269 (br), 2937 (w), 1597 (m), 1503 (s), 1306 (s), 1103 (s), 893 (s); 1H NMR (400MHz, CDCl3) δ 7.40 (1H, ddd, JH-F=10.8, 7.8 Hz, JH-H=0.6 Hz), 6.85 (1H, dd, JH-F=10.9, 7.8 Hz), 6.31 (1H, dd, J=10.0, 2.0 Hz), 6.05 (1H, dd. J=10.0, 2.0 Hz), 4.79 (1H, d, J=11.0 Hz), 4.05 (1H, ddd, J=11.0, 2.0, 2.0 Hz), 3.49 (3H, s), 2.94 (1H, d, J=2.2 Hz); 13C NMR (400 MHz, CDCl3) δ 151.0 (d, JH-F=12.5 Hz), 148.5 (dd, JH-F=12.5,2.9 Hz), 133.2 (dd, JH-F=5.2, 3.6 Hz), 128.9 (dd, JH-F=6.6, 4.4 Hz), 128.0 (d, JH-F=2.2 Hz), 126.5 (dd, JH-F=2.2, 1.5 Hz), 115.1 (d, JH-F=18.3 Hz), 114.8 (d, JH-F=19.8 Hz), 82.3, 72.0, 57.0. HRMS calcd for C11H10O2F2 (M+): 212.0649. Found: 212.0658.

Workup

  1. customTo a flame dried round bottom flask
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 1 hour
  4. customThe solvents were then removed in vacuo
  5. customThe resulting solid was purified by flash chromatography (20% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-276d79634b1e4e7aaeddef081366f7f5
Source dataset
uspto-grants-2008_09
Patent number
US07420003B2

Reaction notes

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