Hydrochloric Acid → 3,3-Dimethylspiro-(cyclopropane-1,1'-indene)-2-carboxylic acid 3-phenoxy-4-fluoro-benzyl ester

HRID 2058454Notes

Reaction equation

HRID 2058454 reaction equation
[O:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:11][OH:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:17][C:18]1([CH3:32])[C:20]2([C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21]2)[CH:19]1[C:29](Cl)=[O:30].N1C=CC=CC=1.Cl>C1(C)C=CC=CC=1.O>[O:1]([C:8]1[CH:9]=[C:10]([CH:13]=[CH:14][C:15]=1[F:16])[CH2:11][O:12][C:29]([CH:19]1[C:20]2([C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:22]=[CH:21]2)[C:18]1([CH3:32])[CH3:17])=[O:30])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 1084583,3-Dimethylspiro[cyclopropane-1,1'-indene]-2-carbonyl chlorideHCID 12874224(4-Fluoro-3-phenoxyphenyl)methanol

Product 1

HCID 127745633,3-Dimethylspiro-(cyclopropane-1,1'-indene)-2-carboxylic acid 3-phenoxy-4-fluoro-benzyl esterYield 86.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent2×

Procedure

5.05 g (0.0232 mol) of 3-phenoxy-4-fluoro-benzyl alcohol and 5.4 g (0.0232 mol) of 3,3-dimethyl-spiro(cyclopropane-1,1'-indene)-2-carboxylic acid chloride were dissolved in 100 ml of anhydrous toluene, and 2.5 g of pyridine, dissolved in 50 ml of toluene, were added dropwise at 20°-25° C., while stirring. The mixture was stirred at 25°-35° C. for a further 3 hours. The reaction mixture was poured into 150 ml of water, to which 5 ml of concentrated hydrochloric acid were added, and the organic phase was separated off and washed again with 100 ml of water. The toluene phase was then dried over sodium sulphate and the solvent was distilled off under a waterpump vacuum. Last residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg. 8.3 g (86.4% of theory) of 3,3-dimethylspiro-(cyclopropane-1,1'-indene)-2-carboxylic acid 3-phenoxy-4-fluoro-benzyl ester were obtained as a viscous oil. The structure was confirmed by the 1H-NMR spectrum.

Workup

  1. additionwere added dropwise at 20°-25° C.
  2. stirringThe mixture was stirred at 25°-35° C. for a further 3 hours
  3. additionwere added
  4. customthe organic phase was separated off
  5. washwashed again with 100 ml of water
  6. dry with materialThe toluene phase was then dried over sodium sulphate
  7. distillationthe solvent was distilled off under a waterpump vacuum
  8. customLast residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg

Sources & evidence

ORD record
ord-4de684ca284c4e35b31d5bab09351785
Source dataset
uspto-grants-1982_03
Patent number
US04317834

Reaction notes

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