Hydrochloric Acid → (3-Dibenzylamino-2-hydroxy-5-methyl-hexyl)-phosphonic acid dimethyl ester

HRID 43312Notes

Reaction equation

HRID 43312 reaction equation
[CH3:1][O:2][P:3]([CH2:7][C:8](=[O:29])[CH:9]([N:14]([CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:10][CH:11]([CH3:13])[CH3:12])(=[O:6])[O:4][CH3:5].C1COCC1.[BH4-].[Na+].Cl>CO>[CH3:1][O:2][P:3]([CH2:7][CH:8]([OH:29])[CH:9]([N:14]([CH2:22][C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:10][CH:11]([CH3:13])[CH3:12])(=[O:6])[O:4][CH3:5]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 72266812(3-Dibenzylamino-5-methyl-2-oxohexyl)-phosphonic acid dimethyl ester

Product 1

HCID 72266810(3-Dibenzylamino-2-hydroxy-5-methyl-hexyl)-phosphonic acid dimethyl esterYield 64.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
-2.5 °C

Procedure

Reaction 3: A mixture of the crude oil (3-dibenzylamino-5-methyl-2-oxohexyl)-phosphonic acid dimethyl ester, i.e., compound 3, obtained in reaction 2, was dissolved in about 10% methanol and about 90% THF (v/v) and cooled at −10° C. NaBH4 (68.58 mmol) was added to the mixture in small portions with vigorous stirring. The mixture was stirred at temperature of −10 to 5° C. for 4 h and HCl 5% (v/v) was added. The reaction mixture was concentrated under reduced pressure. The residual oil was dissolved in ethyl acetate, and washed with 30 ml portions of water. The organic phase was dried over anhydrous Na2SO4 and filtered. The solvent was evaporated off to leave (3-dibenzylamino-2-hydroxy-5-methyl-hexyl)-phosphonic acid dimethyl ester as a crude oil. 31P NMR (at 200 MHz, CDCl3) indicated an 80:20 ratio of 2R,3S (δ 34.53) to 2S,3S (δ 35.15) isomers. The diastereomeric mixture was purified by flash chromatography on silica gel using hexane/ethyl acetate as the eluent to afford compound 2R,3S-4 (20.753 g; 64.9% yield; 31P NMR at 200 MHz, CDCl3; δ 34.61).

Workup

  1. customReaction 3
  2. customobtained in reaction 2
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. dissolutionThe residual oil was dissolved in ethyl acetate
  5. washwashed with 30 ml portions of water
  6. dry with materialThe organic phase was dried over anhydrous Na2SO4
  7. filtrationfiltered
  8. customThe solvent was evaporated off

Sources & evidence

ORD record
ord-b456c4a1369a45f1b371998ab4ecfca5
Source dataset
uspto-grants-2013_09
Patent number
US08536362B2

Reaction notes

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