Dicyclohexylcarbodiimide → (S)alpha-cyano-3-phenoxy-4-fluoro-benzyl(1R,cis,Z)2,2-dimethyl-3-[3-oxo-3-tert.-butoxy-1-propenyl]-cyclopropanecarboxylate

HRID 569540Notes

Reaction equation

HRID 569540 reaction equation
[C:1]([C@@H:3]([OH:18])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:5]=1)#[N:2].[CH3:19][C:20]1([CH3:35])[C@@H:22](/[CH:23]=[CH:24]\[C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[C@H:21]1[C:32](O)=[O:33].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:19][C:20]1([CH3:35])[C@@H:22](/[CH:23]=[CH:24]\[C:25](=[O:31])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[C@H:21]1[C:32]([O:18][C@H:3]([C:1]#[N:2])[C:4]1[CH:9]=[CH:8][C:7]([F:10])=[C:6]([O:11][C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:5]=1)=[O:33]

Participants

6

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 12803645(S)-4-Fluoro-3-phenoxybenzaldehyde-cyanhydrineHCID 13269380(1R,cis,Z) 2,2-dimethyl-3-[3-oxo-3-tert.-butoxy-1-propenyl]-cyclopropane-carboxylic acid

Product 1

HCID 13188405(S)alpha-cyano-3-phenoxy-4-fluoro-benzyl(1R,cis,Z)2,2-dimethyl-3-[3-oxo-3-tert.-butoxy-1-propenyl]-cyclopropanecarboxylateYield 87.3%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-5 °C

Procedure

A mixture of 310 g of (S)α-cyano-3-phenoxy-4-fluoro-benzyl alcohol, 310 g of (1R,cis,Z)2,2-dimethyl-3-[3-oxo-3-tert.-butoxy-1-propenyl]-cyclopropane-carboxylic acid and 1.55 liters of methylene chloride was stirred until total dissolution occured and the mixture was cooled to -5° C. and mixed with a solution of 263.5 g of dicyclohexylcarbodiimide, 3.1 g of 4-dimethylamino-pyridine and 530 ml of methylene chloride. The mixture was stirred at -5° C. for one hour and at room temperature for 3 hours and was vacuum filtered. The filtrate was washed with N hydrochloric acid and then with water, dried and evaporated to dryness under reduced pressure. The residue in 1.185 liters of isopropanol, 80 ml of water and 72 ml of triethylamine was stirred for 36 hours and was vacuum filtered. The product was washed with isopropanol to obtain 518 g of (S)α-cyano-3-phenoxy-4-fluoro-benzyl(1R,cis,Z)2,2-dimethyl-3-[3-oxo-3 -tert.-butoxy-1-propenyl]-cyclopropane-carboxylate melting at 114° C.

Workup

  1. stirringThe mixture was stirred at -5° C. for one hour and at room temperature for 3 hours
  2. filtrationfiltered
  3. washThe filtrate was washed with N hydrochloric acid
  4. dry with materialwith water, dried
  5. customevaporated to dryness under reduced pressure
  6. stirringThe residue in 1.185 liters of isopropanol, 80 ml of water and 72 ml of triethylamine was stirred for 36 hours
  7. filtrationfiltered
  8. washThe product was washed with isopropanol

Sources & evidence

ORD record
ord-113c0f0cf5904d39babb75ad8b6ed119
Source dataset
uspto-grants-1988_03
Patent number
US04732903

Reaction notes

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