Hydrochloric Acid → HCID 66768525, compound

HRID 1865142Notes

Reaction equation

HRID 1865142 reaction equation
CC1OC[C:5]([CH2:25][O:26][P:27](=[O:38])([O:33]C(C)(C)C)[O:28]C(C)(C)C)([CH2:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[CH:11][CH:10]=2)[N:6]=1.Cl.[CH2:40]([OH:42])[CH3:41]>>[P:27]([OH:38])([OH:33])([OH:28])=[O:26].[NH2:6][C:5]([O:42][CH2:40][CH3:41])([CH2:7][CH2:8][C:9]1[CH:10]=[CH:11][C:12]([O:15][CH2:16][CH2:17][O:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)=[CH:13][CH:14]=1)[CH3:25]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 702EthanolHCID 66768403HCID 66768403, compound

Product 1

HCID 66768525HCID 66768525, compound

Conditions

Temperature
50 °C

Procedure

To a solution of (2-methyl-4-{2-[4-(2-phenoxy-ethoxy)-phenyl]-ethyl}-4,5-dihydro-oxazol-4-yl)-methanol (200 mg, 0.56 mmol) and tetrazole (197 mg, 2.81 mmol, 5 eq., recrystallized from toluene) in dry THF (5 ml) was added di-tert-butyl-N,N-diisopropylphosphoramide (561 mg, 2.25 mmol, 4 eq.). After stirring under argon at RT for 3 h, H2O2 (30%, 10 eq.) was slowly added at 0° C. with vigorous stirring. The reaction mixture was stirred for further 30 min, followed by addition of saturated sodium thiosulfate solution (5 ml). The organic layer was separated and the aqueous phase was extracted with ether (3×20 ml). The combined organic extracts were washed with brine, dried over MgSO4, and evaporated to dryness. Purification by flash chromatography (AcOEt/hexane 1:1) afforded phosphoric acid di-tert-butyl ester 2-methyl-4-{2-[4-(2-phenoxy-ethoxy)-phenyl]-ethyl}-4,5-dihydro-oxazol-4-ylmethyl ester as colorles crystals. Finally, to a solution of phosphoric acid di-tert-butyl ester 2-methyl-4-{2-[4-(2-phenoxy-ethoxy)-phenyl]-ethyl}-4,5-dihydro-oxazol-4-ylmethyl ester (150 mg, 0.27 mmol) in ethanol (5 ml) was added conc. HCl (5 ml). The reaction mixture was stirred at 50° C. for 2 hours, then concentrated to dryness. The residue was re-dissolved in AcOEt and precipitated with hexanes. The solid was filtered off, washed with dry ether and dried in vacuo to afford mono-(2-amino-4-{4-[2-phenoxy-ethoxy]-phenyl}-2-ethoxy-butan) phosphate as a colorless powder. ESI+ MS: m/z=410.2 (M−H)+.

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionThe residue was re-dissolved in AcOEt
  3. customprecipitated with hexanes
  4. filtrationThe solid was filtered off
  5. washwashed with dry ether
  6. customdried in vacuo

Sources & evidence

ORD record
ord-cb061fbc9ff6434390c764bba2fa7957
Source dataset
uspto-grants-2009_12
Patent number
US07625950B2

Reaction notes

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