N-methyl-2-pyrrolidone → DiiSopropyl ((1-((trityloxy)methyl)cyclopropoxy)methyl)phosphonate

HRID 1714493Notes

Reaction equation

HRID 1714493 reaction equation
[C:1]([O:20][CH2:21][C:22]1([OH:25])[CH2:24][CH2:23]1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26]N1C(=O)CCC1.CCCCO[P:38]([O:41][CH2:42][CH2:43]CC)([CH3:40])=[O:39].[NH4+].[Cl-].C[C:49]([O:52]C)([CH3:51])[CH3:50]>>[CH:42]([O:41][P:38]([CH2:40][O:25][C:22]1([CH2:21][O:20][C:1]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:23][CH2:24]1)(=[O:39])[O:52][CH:49]([CH3:50])[CH3:51])([CH3:43])[CH3:26]

Participants

6

Reactant 5

HCID 13387N-methyl-2-pyrrolidoneHCID 15413tert-Butyl methyl etherHCID 16994Dibutyl methylphosphonateHCID 25517Ammonium ChlorideHCID 115807541-Trityloxymethyl-cyclopropanol6×

Product 1

HCID 11511792DiiSopropyl ((1-((trityloxy)methyl)cyclopropoxy)methyl)phosphonateYield 71.3%

Conditions

Temperature
-10 °C

Procedure

To the compound of formula (9) (261.25 g, 0.79 mol) obtained by concentration under reduced pressure in Example 2 (it was assumed that the compound of formula (9) was obtained in a yield of 79% starting from Example 1, since the peak area by HPLC was 78.54%) were added NMP [1050 ml, 4 ml/g with respect to the compound of formula (9)] and DBMP (307 g, 1.2 mol). To the reaction mixture was added LTB (107 g, 1.3 mol), which was then stirred under the condition of not exceeding 45° C. After about 6˜19 hours, completion of the reaction was confirmed by HPLC, and 14% aqueous NH4Cl solution [1830 ml, 7 ml/g with respect to the compound of formula (9)] was added thereto to stop the reaction. MTBE [first: 1050 ml, 4 ml/g with respect to the compound of formula (9); second: 520 ml, 2 ml/g with respect to the compound of formula (9)] was added thereto twice for phase-separation. Thus obtained organic layers were combined and washed with 21% aqueous NaCl solution [1650 ml, 6.3 ml/g with respect to the compound of formula (9)]. The remaining organic layer was concentrated under reduced pressure, and heptane [1300 ml, 5 ml/g with respect to the compound of formula (8)] was added thereto. The mixture was cooled to −10° C., and filtered after about 3 hours to give the title compound of formula (10) (586 g, Purity 96.23%, Yield 71.3%) as a solid.

Workup

  1. customwas obtained in a yield of 79%
  2. additionTo the reaction mixture was added LTB (107 g, 1.3 mol), which
  3. customexceeding 45° C
  4. waitAfter about 6˜19 hours
  5. additionwas added
  6. customthe reaction
  7. customtwice for phase-separation
  8. washwashed with 21% aqueous NaCl solution [1650 ml, 6.3 ml/g with respect to the compound of formula (9)]
  9. concentrationThe remaining organic layer was concentrated under reduced pressure, and heptane [1300 ml, 5 ml/g with respect to the compound of formula (8)]
  10. additionwas added
  11. filtrationfiltered after about 3 hours

Sources & evidence

ORD record
ord-8a2b61f1ca034640879028829ca1f16a
Source dataset
uspto-grants-2010_09
Patent number
US07795463B2

Reaction notes

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