HCID 22860715, compound → HCID 9909972, compound

HRID 862684Notes

Reaction equation

HRID 862684 reaction equation
[F:1][C:2]([F:32])([F:31])[C:3]1[CH:4]=[C:5]([CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1)[CH2:6][O:7][C@@H:8]1[O:13][C@H:12]([CH3:14])[CH2:11][N:10](CC=C)[C@@H:9]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh].C(#N)C.O>[F:32][C:2]([F:1])([F:31])[C:3]1[CH:4]=[C:5]([CH:24]=[C:25]([C:27]([F:28])([F:29])[F:30])[CH:26]=1)[CH2:6][O:7][C@@H:8]1[O:13][C@H:12]([CH3:14])[CH2:11][NH:10][C@@H:9]1[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

4

Reactant 1

HCID 22860715HCID 22860715, compound

Product 1

HCID 9909972HCID 9909972, compoundYield 64%

Reagents, catalysts & solvents 2

HCID 84599Chlorotris(triphenylphosphine)rhodium(I)CatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Procedure

A solution of 115 mg (0.25 mmol) of the 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-4-(2-propenyl)-6-(R)-methyl morpholine (from Example 23, Step A) and 230 mg (0.25 mmol) of tris(triphenylphosphine)rhodium chloride in 15 mL of 4:1 v/v acetonitrile/water was heated at reflux for 30 min. The reaction was cooled and partitioned between 50 mL of ethyl acetate and 15 mL of water. The layers were separated and the organic layer was dried over magnesium sulfate. The aqueous layer was extracted with 2×25 mL of ethyl acetate; the extracts were dried and combined with the original organic layer. The combined organics were concentrated in vacuo. The residue was filtered through a pad of silica gel (~20 g) using 2:1 v/v ether/hexanes as the solvent. The filtrate was concentrated; flash chromatography on 5 g of silica gel using 17:3 v/v hexanes/ether as the eluant afforded 67 mg (64%) of 2-(R)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenyl-6-(R)-methyl morpholine as an oil.

Workup

  1. temperatureat reflux for 30 min
  2. temperatureThe reaction was cooled
  3. custompartitioned between 50 mL of ethyl acetate and 15 mL of water
  4. customThe layers were separated
  5. dry with materialthe organic layer was dried over magnesium sulfate
  6. extractionThe aqueous layer was extracted with 2×25 mL of ethyl acetate
  7. customthe extracts were dried
  8. concentrationThe combined organics were concentrated in vacuo
  9. filtrationThe residue was filtered through a pad of silica gel (~20 g)
  10. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-8e13025933ce452a90ed72a5c3ec3d4b
Source dataset
uspto-grants-1998_02
Patent number
US05719147

Reaction notes

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