Triethyl phosphonoacetate → HCID 121336084, compound

HRID 524478Notes

Reaction equation

HRID 524478 reaction equation
C(OP([CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])(OCC)=O)C.[H-].[Na+].C([O:20][C@H:21]1[CH2:38][CH2:37][C@@:36]2([CH3:39])[C@@H:23]([CH2:24][CH2:25][C@:26]3([CH3:49])[C@@H:35]2[CH2:34][CH2:33][C@H:32]2[C@@:27]3([CH3:48])[CH2:28][CH2:29][C@@:30]3([CH:46]=O)[CH2:42][CH2:41][C:40]([CH:43]([CH3:45])[CH3:44])=[C:31]32)[C:22]1([CH3:51])[CH3:50])(=O)C>CN(C)C=O.O1CCCC1>[OH:20][C@H:21]1[CH2:38][CH2:37][C@@:36]2([CH3:39])[C@@H:23]([CH2:24][CH2:25][C@:26]3([CH3:49])[C@@H:35]2[CH2:34][CH2:33][C@H:32]2[C@@:27]3([CH3:48])[CH2:28][CH2:29][C@@:30]3(/[CH:46]=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH2:42][CH2:41][C:40]([CH:43]([CH3:44])[CH3:45])=[C:31]32)[C:22]1([CH3:50])[CH3:51]

Participants

6

Reactant 3

HCID 13345Triethyl phosphonoacetateHCID 24758Sodium hydrideHCID 89261519HCID 89261519, compound

Product 1

HCID 121336084HCID 121336084, compoundYield 69.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of ethyl 2-(diethoxyphosphoryl)acetate (7.80 g, 34.8 mmol) in anhydrous N,N-Dimethylformamide (DMF) (20 ml) and Tetrahydrofuran (THF) (10 ml) stirred under nitrogen at 0° C. was added NaH (1.288 g, 32.2 mmol) dropwise during 5 min and stirred for 10 mins. The solution was warmed to rt and stirred for 30 mins before (3aS,5aR,5bR,7aR,9S,11aR,11bR,13aS)-3a-formyl-1-isopropyl-5a,5b,8,8,11a-pentamethyl-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-9-yl acetate (4.2 g, 8.70 mmol) was added to above mixture. After sitting overnight, the reaction was quenched by water and washed with saturated NaHCO3, water and brine. The organic fraction was dried over sodium sulfate, filtered and concentrated to give a residue, which was purified on a silica gel column (petrol ether/EtOAc=10:1) to obtain the pure product (E)-ethyl 3-((3aR,5aR,5bR,7aR,9S,11aR,11bR,13aS)-9-hydroxy-1-isopropyl-5a,5b,8,8,11a-pentamethyl-3,3a,4,5,5a,5b,6,7,7a,8,9,10,11,11a,11b,12,13,13a-octadecahydro-2H-cyclopenta[a]chrysen-3a-yl)acrylate (3.1 g, 69%) as a white foam. 1H NMR (400 MHz, CHLOROFORM-d) δ=7.01-6.84 (m, 2H), 5.64 (d, J=16.1 Hz, 1H), 4.20 (q, J=7.3 Hz, 2H), 3.26-3.07 (m, 3H), 2.40-2.11 (m, 5H), 2.08-1.91 (m, 2H), 1.89-0.61 (m, 43H).

Workup

  1. stirringstirred for 10 mins
  2. temperatureThe solution was warmed to rt
  3. additionwas added to above mixture
  4. customthe reaction was quenched by water
  5. washwashed with saturated NaHCO3, water and brine
  6. dry with materialThe organic fraction was dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a residue, which
  10. customwas purified on a silica gel column (petrol ether/EtOAc=10:1)

Sources & evidence

ORD record
ord-77490ea397cd40b9af1f8b60537403cd
Source dataset
uspto-grants-2016_05
Patent number
US09340513B2

Reaction notes

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