Hydrochloric Acid → HCID 178454806, compound

HRID 1400004Notes

Reaction equation

HRID 1400004 reaction equation
[P:1]([O-])([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[K+].Cl>O>[C:9]([O:8][PH:1](=[O:2])[O:3][C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:12])([CH3:11])[CH3:10]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 23674467Potassium di-tert-butyl phosphate

Product 1

HCID 178454806HCID 178454806, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Potassium di-tert-butyl phosphate (45 g) was dissolved in water (160 mL). Hydrochloric acid (1M, aq) was added until the pH was ˜3. The resultant precipitate was collected by filtration, washed with water, and dried under vacuum overnight to give di-tert-butyl phosphonic acid as a white solid. Then, to a suspension of i (18.68 g, 39.28 mmol), triphenylphosphine (17.51 g, 66.78 mmol), and di-tert-butyl hydrogen phosphate (10.73 g, 51.06 mmol) in THF and triphenylphosphine were suspended in anhydrous THF (200 mL). A solution of DIAD (13.5 g, 66.78 mmol) in THF (20 mL) was added dropwise. The mixture was stirred at room temperature and monitored by LCMS to completion then was concentrated under reduced pressure. Et2O (300 mL) was added and the mixture sonicated, resulting in a bright white solid, which was filtered, washed with Et2O (100 mL) and air dried. The filtrate also contained some product. After concentration to 150 mL the filtrate was chilled in ice, yielding more solid material. The solids were collected, redissolved in DCM, and plugged (50-100% EtOAc/DCM to remove Mitsonobu by-products then 10% MeOH/DCM to elute the desired product. After concentrating the relevant fraction to a white solid, this material was recrystallized from DCM/ether/heptane, filtered, washed with heptane, and dried overnight to give ii as a white solid (17.09 g, 64%). 1H NMR (400 MHz) δ 9.41 (s, 2H); 8.83 (d, J=4.4 Hz, 1H); 8.53 (d, J=8 Hz, 1H); 8.43 (d, J=1.2 Hz, 1H); 8.21 (d, J=1.2 Hz, 1H); 8.01 (dt, J=8, 1.6 Hz, 1H); 7.46 (dd, J=7.2, 4.8 Hz); 5.43 (m, 1H); 5.16 (s, 2H); 4.38 (s, 2H); 3.39 (q, J=7.2 Hz, 2H); 3.32 (br s, 2H); 2.55 (s, 3H); 1.64 (d, J=6.8 Hz, 3H); 1.38 (s, 9H); 1.36 (s, 9H); 1.14 (t, J=7.2 Hz). MS: 667.78 (M+H)+. Chiral HPLC: Column. Chirapak IC, 0.46 cm×25 cm; 25 min isocratic gradent 100% MeOH retention time=17.12 min.

Workup

  1. filtrationThe resultant precipitate was collected by filtration
  2. washwashed with water
  3. customdried under vacuum overnight

Sources & evidence

ORD record
ord-5f590429a69e4f12a532e276abfe3836
Source dataset
uspto-grants-2014_12
Patent number
US08906902B2

Reaction notes

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