Sodium Fluoride → HCID 58385972, compound

HRID 1895878Notes

Reaction equation

HRID 1895878 reaction equation
[C:1]1([C@H:7]([NH2:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Al](C)C.[F:14][C:15]1([F:22])[CH2:21][CH2:20][CH2:19][CH:18]2[CH:16]1[O:17]2.[F-].[Na+]>ClCCl>[F:14][C:15]1([F:22])[CH2:21][CH2:20][CH2:19][C@H:18]([NH:9][C@@H:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH3:8])[C@H:16]1[OH:17]

Participants

6

Reactant 4

HCID 5235Sodium FluorideHCID 6431891-Phenethylamine, (+)-HCID 16682925TrimethylaluminumHCID 534020142,2-Difluoro-7-oxabicyclo[4.1.0]heptane

Product 1

HCID 58385972HCID 58385972, compoundYield 29%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

A solution of (1R)-1-phenylethanamine (22, 72 mL, 0.57 mol) in dichloromethane (200 mL) was cooled to 0° C. and treated with trimethylaluminum (260 mL, 0.52 mol) and the resulting solution was stirred for 1 hour at 0° C. To this solution was added a solution of 2,2-difluoro-7-oxabicyclo[4.1.0]heptane (66 g, 0.49 mol) in dichloromethane (200 mL) and the resulting mixture stirred at 0° C. for 3 hours. The reaction was then warmed to ambient temperature for 16 hours. The reaction was cooled to 0° C., treated with 103 g of sodium flouride and then quenched with water (90 mL, slow addition). The reaction was warmed to ambient temperature, the solids filtered and the solution evaporated in vacuo, Purification by flash chromatography (50-100% ethyl acetate in hexanes) gave 36.3 g (29%) of (1S,6R)-2,2-difluoro-6-{[(1R)-1-phenylethyl]amino}cyclohexanol 23 (plus 32 g of 1R,6S diastereomer) as a white solid: 1H NMR (500 MHz, CDCl3) δ 7.32 (5H, s), 3.90 (1H, q, =6.6 Hz), 3.39 (1H, ddd, J=19.8, 9.8, 4.2 Hz), 2.70 (1H, m), 2.11 (1H, m), 1.80 (1H, m), 1.62 (2H, m), 1.43 (1H, m), 1.36 (3H, d, J=6.6 Hz), 0.96 (1H, m).

Workup

  1. stirringthe resulting mixture stirred at 0° C. for 3 hours
  2. temperatureThe reaction was then warmed to ambient temperature for 16 hours
  3. temperatureThe reaction was cooled to 0° C.
  4. customquenched with water (90 mL, slow addition)
  5. temperatureThe reaction was warmed to ambient temperature
  6. filtrationthe solids filtered
  7. customthe solution evaporated in vacuo, Purification by flash chromatography (50-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-deb7f9b1125745798c27bb725c2d0c05
Source dataset
uspto-grants-2013_08
Patent number
US08518911B2

Reaction notes

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