4-Hydroxybenzaldehyde → 4-((4-Phenyl-5-(trifluoromethyl)thiophen-2-yl)methoxy)benzaldehyde

HRID 898207Notes

Reaction equation

HRID 898207 reaction equation
OCC1C=CC=C[C:4]=1[C:9]1[S:10][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:12][CH:13]=1.[OH:18][C:19]1[CH:26]=[CH:25][C:22]([CH:23]=[O:24])=[CH:21][CH:20]=1.CCOC(/N=N/C(O[CH2:37][CH3:38])=O)=O>C1COCC1>[C:38]1([C:12]2[CH:13]=[C:9]([CH2:4][O:18][C:19]3[CH:26]=[CH:25][C:22]([CH:23]=[O:24])=[CH:21][CH:20]=3)[S:10][C:11]=2[C:14]([F:15])([F:16])[F:17])[CH:37]=[CH:12][CH:13]=[CH:9][CH:4]=1

Participants

5

Reactant 3

HCID 1264-HydroxybenzaldehydeHCID 5462977Diethyl azodicarboxylateHCID 692246282-Hydroxymethylphenyl-5-trifluoromethyl-thiophene

Product 1

HCID 111875844-((4-Phenyl-5-(trifluoromethyl)thiophen-2-yl)methoxy)benzaldehydeYield 184%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1.95 g (7.5 mmol) of 2-hydroxymethyl-4-phenyl-5-trifluoromethyl-thiophene (from Step A), 925 mg (7.6 mmol) of 4-hydroxybenzaldehyde and 3.0 g (11.4 mmol) of triphenylphosphene in 40 mL of THF at 0° C. was treated with 2.0 g (11.4 mmol) of diethylazodicarboxylate. The resulting mixture was warmed to rt, stirred for 2 h, then concentrated. Chromatography on a Biotage 75S cartridge using 9:1 v/v heptane/EtOAc as the eluant afforded 2.5 g of impure title compound. Chromatography on a Biotage 40M cartridge using 19:1 v/v hexanes/EtOAc (1 L), then 4:1 v/v hexanes/EtOAc (1 L) as the eluant afforded 1.65 g (60%) of the title compound: 1H NMR (500 Mhz) δ 5.32 (s, 2H), 7.10 (d, J=8.5, 2H), 7.12 (s, 1H), 7.41-7.43 (5H), 7.85-7.90 (2H), 9.92 (s, 1H).

Workup

  1. concentrationconcentrated

Sources & evidence

ORD record
ord-79502bbcfcc74e55b4a58ab2c5814468
Source dataset
uspto-grants-2008_04
Patent number
US07351725B2

Reaction notes

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