Triphenylphosphine → (R)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-benzonitrile

HRID 245087Notes

Reaction equation

HRID 245087 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].[CH3:13][C:14]1([CH3:21])[O:18][C@H:17]([CH2:19]O)[CH2:16][O:15]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH3:13][C:14]1([CH3:21])[O:18][C@H:17]([CH2:19][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])[CH2:16][O:15]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 736056(R)-SolketalHCID 5462977Diethyl azodicarboxylateHCID 597599503-Ethyl-4-hydroxy-5-methylbenzonitrile

Product 1

HCID 67491300(R)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-benzonitrileYield 90.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-ethyl-4-hydroxy-5-methyl-benzonitrile (2.89 g, 17.9 mmol) in THF (80 mL), (R)-(2,2-dimethyl-[1,3]dioxolan-4-yl)methanol (2.84 g, 21.5 mmol) followed by triphenylphosphine (5.81 g, 21.5 mmol) is added. The mixture is cooled with an ice-bath before DEAD (9.36 g, 21.5 mmol) is added dropwise. The mixture is stirred at rt for 1 h, the solvent is removed in vacuo and the residue is purified by CC on silica gel eluting with heptane:EA 85:15 to give (R)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-benzonitrile (4.45 g) as a pale yellow oil; LC-MS**: tR=0.75 min, [M+1]+=not detected; 1H NMR (CDCl3): δ1.25 (t, J=7.5 Hz, 3H), 1.44 (s, 3H), 1.49 (s, 3H), 2.34 (s, 3H), 2.65-2.77 (m, 2H), 3.80-3.90 (m, 2H), 3.94-4.00 (m, 1H), 4.21 (t, J=7.3 Hz, 1H), 4.52 (quint, J=5.8 Hz, 1H), 7.35 (s, 1H), 7.38 (s, 1H).

Workup

  1. additionis added
  2. additionis added dropwise
  3. customthe solvent is removed in vacuo
  4. customthe residue is purified by CC on silica gel eluting with heptane:EA 85:15

Sources & evidence

ORD record
ord-1bee3782d6c349e68103b588330ff481
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

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