Lithium Hydroxide → 3-{N-[1(S)-(3,4-dichlorophenyl)ethyl]amino}-2(S)-hydroxy-propyl-(cyclohex-3-enylmethyl)-phosphinic acid

HRID 1492971Notes

Reaction equation

HRID 1492971 reaction equation
[OH-].[Li+].C([O:5][P:6]([CH2:15][C@@H:16]([OH:18])[CH3:17])([CH2:8][CH:9]1[CH2:14][CH2:13][CH:12]=[CH:11][CH2:10]1)=[O:7])C.BrCC1CCC=CC1.C(OP(C(OCC)(OCC)C)=O)C.C(OP(C[C@@H](O)CCl)(CC1CCC=CC1)=O)C.[Cl:57][C:58]1[CH:59]=[C:60]([C@@H:65]([NH2:67])[CH3:66])[CH:61]=[CH:62][C:63]=1[Cl:64]>O.C(O)C>[Cl:57][C:58]1[CH:59]=[C:60]([C@@H:65]([NH:67][CH2:17][C@H:16]([OH:18])[CH2:15][P:6]([CH2:8][CH:9]2[CH2:14][CH2:13][CH:12]=[CH:11][CH2:10]2)(=[O:7])[OH:5])[CH3:66])[CH:61]=[CH:62][C:63]=1[Cl:64]

Participants

9

Reactant 6

HCID 3939Lithium HydroxideHCID 5654734-(Bromomethyl)cyclohexeneHCID 793512(S)-1-(3,4-Dichlorophenyl)ethanamineHCID 541698053-chloro-2(R)-hydroxy-propyl-(cyclohex-3-enylmethyl)phosphinic acid ethyl esterHCID 867483482(S)-hydroxy-propyl-(cyclohex-3-enylmethyl)-phosphinic acid ethyl esterHCID 178476820HCID 178476820, compound

Product 1

HCID 599034363-{N-[1(S)-(3,4-dichlorophenyl)ethyl]amino}-2(S)-hydroxy-propyl-(cyclohex-3-enylmethyl)-phosphinic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of 0.13 g of lithium hydroxide in 3 ml of water is added to a solution in 5 ml of ethanol of 1.1 g of 3-{N-1(S)-(3,4-dichlorophenyl)ethyl]amino}-2(S)-hydroxy-propyl-(cyclohex-3-enylmethyl)-phosphinic acid ethyl ester [obtainable as described in Example 2 starting from bromomethylcyclohex-3-ene and 1,1-diethoxyethylphosphinic acid ethyl ester via 3-chloro-2(R)-hydroxy-propyl-(cyclohex-3-enylmethyl)-phosphinic acid ethyl ester and further reaction thereof with 1(S)-(3,4-dichlorophenyl)ethylamine] and the mixture is heated at 60° for 24 hours, then cooled to room temperature and concentrated by evaporation under reduced pressure. The residue is taken up in water, rendered neutral with aqueous phosphoric acid solution and again concentrated by evaporation under reduced pressure. The white solid that remains behind is taken up in hot methanol and filtered. Removal of the methanol yields a hygroscopic solid which, after crystallisation from cyclohexane/petroleum ether (60°-80°), yields 3-{N-[1(S)-(3,4-dichlorophenyl)ethyl]amino}-2(S)-hydroxy-propyl-(cyclohex-3-enylmethyl)-phosphinic acid in the form of a hygroscopic solid; 1H-NMR spectrum (in CD3OD): δ=7.68 (1H), 7.58 (1H), 7.40 (1H), 6.60 (2H, CH=CH), 4.22 (1H,q,CH), 4.13 (1H,m), 2.97 (1H, dd, CHN), 2.63 (1H, dd,CHN), 2.33-1.21 (14H,m). The hydrochloride melts at 105°-206°.

Workup

  1. concentrationconcentrated by evaporation under reduced pressure
  2. concentrationagain concentrated by evaporation under reduced pressure
  3. filtrationfiltered
  4. customRemoval of the methanol
  5. customyields a hygroscopic solid which
  6. customafter crystallisation from cyclohexane/petroleum ether (60°-80°)

Sources & evidence

ORD record
ord-795044bdd91f42f0bf9d16a0bd9ccb8b
Source dataset
uspto-grants-1994_12
Patent number
US05376684

Reaction notes

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