Diisopropylethylamine → Benzyl 2-(((4-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-2-butenyl)hydroxyphosphinyl)methyl)-4-phenylbutanoate

HRID 1489789Notes

Reaction equation

HRID 1489789 reaction equation
[OH:1][PH:2]([CH2:4][CH:5]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)=[O:7])=[O:3].C(N(C(C)C)CC)(C)C.Br[CH2:34][CH:35]=[CH:36][CH2:37][N:38]1[C:42](=[O:43])[C:41]2=[CH:44][CH:45]=[CH:46][CH:47]=[C:40]2[C:39]1=[O:48]>ClCCl>[O:48]=[C:39]1[C:40]2[C:41](=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:42](=[O:43])[N:38]1[CH2:37][CH:36]=[CH:35][CH2:34][P:2]([CH2:4][CH:5]([CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:6]([O:8][CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)=[O:7])([OH:1])=[O:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 534234322-(4-Bromobut-2-en-1-yl)-1H-isoindole-1,3(2H)-dioneHCID 178525066HCID 178525066, compound

Product 1

HCID 70079492Benzyl 2-(((4-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)-2-butenyl)hydroxyphosphinyl)methyl)-4-phenylbutanoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dichloromethane (30 mL) was added to (+)-benzyl 2-((hydroxyphosphinyl)methyl)-4-phenylbutanoate (8.10 g, 24.4 mmol) and 4Å molecular sieves (5.0 g). Diisopropylethylamine (4.70 mL, 3.49 g, 27.0 mmol) was added over 5 min. After cooling the reaction mixture in an ice bath, O,N-bis(trimethylsilyl)acetamide (17.7 mL, 14.6 g, 71.6 mmol) was added in one portion, followed in 10 min by N-(4-bromo-2-butenyl)phthalimide (8.80 g, 31.4 mmol). The mixture was allowed to slowly warm to room temperature and stirred for 20 h before being filtered. The sieve particles were rinsed with ethyl acetate (100 mL) and the filtrate was washed with 2N aqueous hydrochloric acid (2×50 mL) and saturated aqueous sodium chloride (25 mL). The aqueous layers were extracted in succession with ethyl acetate (50 mL). The organic layers were dried (sodium sulfate), decanted, and evaporated to give 15.66 g of almost colorless syrup containing benzyl 2-(((4-(1,3-dihydro-1,3-dioxo-2M-isoindol-2-yl)-2-butenyl)hydroxyphosphinyl)methyl)-4-phenylbutanoate.

Workup

  1. temperatureAfter cooling the reaction mixture in an ice bath
  2. filtrationbefore being filtered
  3. washThe sieve particles were rinsed with ethyl acetate (100 mL)
  4. washthe filtrate was washed with 2N aqueous hydrochloric acid (2×50 mL) and saturated aqueous sodium chloride (25 mL)
  5. extractionThe aqueous layers were extracted in succession with ethyl acetate (50 mL)
  6. dry with materialThe organic layers were dried (sodium sulfate)
  7. customdecanted
  8. customevaporated
  9. customto give 15.66 g of almost colorless syrup

Sources & evidence

ORD record
ord-1704f5bd28bf45358f98dc2f8e12fe2e
Source dataset
uspto-grants-1997_10
Patent number
US05679700

Reaction notes

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