Triethylamine → Benzyl [hydroxy-(4-phenylbutyl)phosphinyl] acetate

HRID 2351580Notes

Reaction equation

HRID 2351580 reaction equation
[OH:1][P:2]([CH2:14][C:15]([OH:17])=[O:16])([CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:3].C(N(CC)CC)C.[CH2:25](OC(Cl)=O)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>O1CCCC1>[OH:3][P:2]([CH2:14][C:15]([O:17][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:16])([CH2:4][CH2:5][CH2:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:1]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10387Benzyl chloroformateHCID 13102401((4-Phenylbutyl)hydroxyphosphoryl)acetic acid

Product 1

HCID 13187470Benzyl [hydroxy-(4-phenylbutyl)phosphinyl] acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a well stirred solution of [hydroxy-(4-phenylbutyl)phosphinyl]acetic acid (prepared as described in Example 23 of U.S. Pat. No. 4,602,092) (422.5 g, 1.65 mole) in tetrahydrofuran (4700 ml, alumina purified) maintained at -5° C. to -10° C. was gradually added triethylamine (290 ml, 2.08 mole). This was then followed by the dropwise addition of a solution of benzylchloroformate (275 ml, 1.93 mole) in purified tetrahydrofuran (1320 ml). After removing the cooling bath, stirring was continued for three hours. After this time, the reaction mixture was filtered. The solids were washed with ethyl acetate (2×1000 ml). The combined filtrates were concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (4000 ml) and washed with water (2×1000 ml), 2.5% hydrochloric acid (2×600 ml) and brine (2×1000 ml). The organic phase was dried over magnesium sulfate, filtered and concentrated. The residue was triturated with 1:1 ether/hexane (2×500 ml) and collected by filtration. The solid was washed on the frit with 1:1 ether/hexane then dried in vacuo at 30° C. overnight to yield 509 g of colorless crystalline product m.p. 68°-70° C.

Workup

  1. customAfter removing the cooling bath
  2. filtrationAfter this time, the reaction mixture was filtered
  3. washThe solids were washed with ethyl acetate (2×1000 ml)
  4. concentrationThe combined filtrates were concentrated in vacuo
  5. dissolutionThe resultant residue was dissolved in ethyl acetate (4000 ml)
  6. washwashed with water (2×1000 ml), 2.5% hydrochloric acid (2×600 ml) and brine (2×1000 ml)
  7. dry with materialThe organic phase was dried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was triturated with 1:1 ether/hexane (2×500 ml)
  11. filtrationcollected by filtration
  12. washThe solid was washed on the frit with 1:1 ether/hexane
  13. customthen dried in vacuo at 30° C. overnight

Sources & evidence

ORD record
ord-92b6356665134304901afaec8cd0a556
Source dataset
uspto-grants-1989_10
Patent number
US04873356

Reaction notes

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