Trimethyl phosphonoacetate → HCID 90408952, compound

HRID 1855103Notes

Reaction equation

HRID 1855103 reaction equation
[CH3:1][O:2][C:3]([CH2:5]P(OC)(OC)=O)=[O:4].C1CCN2C(=NCCC2)CC1.[Li+].[Cl-].[O:25]([C:32]1[CH:33]=[C:34]([C:38]23[CH2:45][CH2:44][C:41]([CH2:46][CH2:47][CH2:48][CH:49]=O)([CH2:42][CH2:43]2)[CH2:40][O:39]3)[CH:35]=[CH:36][CH:37]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>CC#N>[O:25]([C:32]1[CH:33]=[C:34]([C:38]23[CH2:45][CH2:44][C:41]([CH2:46][CH2:47][CH2:48]/[CH:49]=[CH:5]/[C:3]([O:2][CH3:1])=[O:4])([CH2:42][CH2:43]2)[CH2:40][O:39]3)[CH:35]=[CH:36][CH:37]=1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

6

Reactant 4

HCID 80029Trimethyl phosphonoacetateHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 433294Lithium ChlorideHCID 90408321HCID 90408321, compound2×

Product 1

HCID 90408952HCID 90408952, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

Trimethyl phosphonoacetate (47 mg, 0.26 mmol) and DBU (39 mg, 0.26 mmol) were successively added to a 0° C. solution of LiCl (11 mg; 0.26 mmol) in MeCN (0.6 mL) under argon. The reaction mixture was stirred at 0° C. for 30 min, after which a solution of 120A compound [4-(1-(3-phenoxy-phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)butanal] (60 mg, 0.171 mmol) in MeCN (0.5 mL) was added. The reaction mixture was stirred at rt for 2 h, then was concentrated in vacuo. The residue was diluted with ether and successively washed with 1N aq. HCl, sat′d aq. NaHCO3, water and brine, dried (MgSO4), filtered and concentrated in vacuo. The crude product was chromatographed (SiO2; continuous gradient of EtOAc/hexanes from 0 to 40%) to give the title compound as a white solid (65 mg, 89%). [MS+H]+=407, 1H NMR (400 MHz, CDCl3) δ 7.29-7.19 (m, 3H), 7.10-6.97 (m, 3H), 6.95-6.88 (m, 2H), 6.87-6.83 (m, 1H), 6.77 (ddd, J=8.0, 2.5, 0.9 Hz, 1H), 5.75 (dt, J=15.6, 1.5 Hz, 1H), 3.72 (s, 2H), 3.66 (s, 3H), 2.11 (qd, J=7.2, 1.5 Hz, 2H), 1.93 (dd, J=9.5, 5.3 Hz, 4H), 1.67-1.51 (m, 4H), 1.40-1.25 (m, 2H), 1.14-1.02 (m, 2H).

Workup

  1. stirringThe reaction mixture was stirred at rt for 2 h
  2. concentrationwas concentrated in vacuo
  3. additionThe residue was diluted with ether
  4. washsuccessively washed with 1N aq. HCl
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was chromatographed (SiO2; continuous gradient of EtOAc/hexanes from 0 to 40%)

Sources & evidence

ORD record
ord-67065cb528e54474bd5d30d506aa84a2
Source dataset
uspto-grants-2015_02
Patent number
US08962660B2

Reaction notes

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