Triphenylphosphine → 4-(2,2-Dimethyl-[1,3]dioxan-5-ylmethoxy)-3-ethyl-5-methyl-benzonitrile

HRID 2037340Notes

Reaction equation

HRID 2037340 reaction equation
[CH2:1]([C:3]1[CH:4]=[C:5]([CH:8]=[C:9]([CH3:12])[C:10]=1[OH:11])[C:6]#[N:7])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:32][C:33]1([CH3:41])[O:38][CH2:37][CH:36]([CH2:39]O)[CH2:35][O:34]1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1.C1(C)C=CC=CC=1>[CH3:32][C:33]1([CH3:41])[O:38][CH2:37][CH:36]([CH2:39][O:11][C:10]2[C:9]([CH3:12])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=2[CH2:1][CH3:2])[CH2:35][O:34]1

Participants

7

Reactant 4

HCID 11776TriphenylphosphineHCID 3584869(2,2-Dimethyl-1,3-dioxan-5-yl)methanolHCID 5462977Diethyl azodicarboxylateHCID 597599503-Ethyl-4-hydroxy-5-methylbenzonitrile

Product 1

HCID 686289194-(2,2-Dimethyl-[1,3]dioxan-5-ylmethoxy)-3-ethyl-5-methyl-benzonitrileYield 27.8%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-ethyl-4-hydroxy-5-methyl-benzonitrile (480 mg, 2.98 mmol) in THF (10 mL), triphenylphosphine (1.17 g, 4.47 mmol) and (2,2-dimethyl-[1,3]dioxan-5-yl)-methanol (478 mg, 3.28 mmol) is added. The mixture is cooled to 4° C. before DEAD (1.94 g, 4.47 mmol, 2.05 mL of a 40% solution in toluene) is added. Stirring is continued at 4° C. for 15 min, then at rt for 1 h. The solvent is removed in vacuo and the crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 4-(2,2-dimethyl-[1,3]dioxan-5-ylmethoxy)-3-ethyl-5-methyl-benzonitrile (240 mg) as a yellow oil; LC-MS: tR=1.04 min; [M+1+CH3CN]+=330.97. To a solution of this material (240 mg, 829 μmol) in methanol (5 mL), hydroxylamine hydrochloride (86 mg, 1.24 mmol) and NaHCO3 (104 mg, 1.24 mmol) is added. The mixture is stirred at 60° C. for 5 h before it is diluted with EA and washed with water. The org. extract is dried over MgSO4, filtered, concentrated and dried to give the title compound (280 mg) as a pale yellow oil; LC-MS: tR=0.72 min; [M+1+CH3CN]+=323.01.

Workup

  1. additionis added
  2. waitat rt for 1 h
  3. customThe solvent is removed in vacuo
  4. customthe crude product is purified by CC on silica gel eluting with heptane:EA 9:1

Sources & evidence

ORD record
ord-d55b155ff69e4e4db20e60494dc3791a
Source dataset
uspto-grants-2013_11
Patent number
US08575200B2

Reaction notes

Loading…