Water → cis-4-(4-Bromophenoxy)tetrahydrofuran-3-amine

HRID 2360323Notes

Reaction equation

HRID 2360323 reaction equation
[N:1]([C@H:4]1[C@@H:8]([O:9][C:10]2[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][CH:11]=2)[CH2:7][O:6][CH2:5]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>O1CCCC1>[Br:16][C:13]1[CH:14]=[CH:15][C:10]([O:9][C@H:8]2[CH2:7][O:6][CH2:5][C@H:4]2[NH2:1])=[CH:11][CH:12]=1

Participants

5

Reactant 3

HCID 962WaterHCID 11776TriphenylphosphineHCID 86653048cis-3-Azido-4-(4-bromophenoxy)tetrahydrofuran

Product 1

HCID 67193588cis-4-(4-Bromophenoxy)tetrahydrofuran-3-amineYield 59.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of cis-3-azido-4-(4-bromophenoxy)tetrahydrofuran (286.7 g, 1.01 mol) in tetrahydrofuran (1.25 L) was cooled to 0° C. and treated with triphenylphosphine (278 g, 1.06 mol). The reaction was allowed to warm to room temperature and stirred for 18 hours. Water (53 mL) was added and the reaction was stirred at room temperature for 66 hours. Solvent was removed under reduced pressure and the residue was mixed with diethyl ether. The supernatant was decanted and concentrated in vacuo, providing a residue, which was filtered through a short plug of silica gel (Gradient: 0% to 5% methanol in methylene chloride) to afford cis-4-(4-bromophenoxy)tetrahydrofuran-3-amine (155 g) and 366 grams of impure product. An acid/base extraction was carried out on the impure material, providing additional product (48.5 g). Total yield: 203.5 g, 0.788 mol, 68% over four steps. 1H NMR (300 MHz, CDCl3) δ 3.6 (m, 1H), 3.7 (m, 1H), 3.9 (m, 1H), 4.0 (m, 1H), 4.1 (m, 1H), 4.6 (m, 1H), 6.8 (m, 2H), 7.3 (m, 2H).

Workup

  1. stirringthe reaction was stirred at room temperature for 66 hours
  2. customSolvent was removed under reduced pressure
  3. additionthe residue was mixed with diethyl ether
  4. customThe supernatant was decanted
  5. concentrationconcentrated in vacuo
  6. customproviding a residue, which
  7. filtrationwas filtered through a short plug of silica gel (Gradient: 0% to 5% methanol in methylene chloride)

Sources & evidence

ORD record
ord-48188068d6fd488db8339fc564f38f6d
Source dataset
uspto-grants-2014_04
Patent number
US08686043B2

Reaction notes

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