Tetrahydrofuran → (E,E)-5-[6-[2-methoxy-4-(methoxycarbonylvinyl)phenoxy]oxyhexyl]-2-[6-[3-(3-methoxy-4-butoxyphenyl)acryloyloxy]oxyhexyl]benzoic acid 11-(2-methylacryloyloxy)undecyl ester

HRID 2308118Notes

Reaction equation

HRID 2308118 reaction equation
[CH3:1][C:2](=[CH2:49])[C:3]([O:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:18](=[O:48])[C:19]1[CH:24]=[C:23]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][O:31][O:32][C:33]2[CH:38]=[CH:37][C:36](/[CH:39]=[CH:40]/[C:41]([O:43][CH3:44])=[O:42])=[CH:35][C:34]=2[O:45][CH3:46])C=CC=1O)=[O:4].C[O:51][C:52](=[O:71])[CH:53]=[CH:54][C:55]1[CH:60]=[CH:59][C:58]([O:61][CH2:62][CH2:63][CH2:64][CH2:65]CCO)=[C:57]([O:69][CH3:70])[CH:56]=1.C(P([CH2:81][CH2:82][CH2:83][CH3:84])CCCC)CCC.N(C(N1[CH2:102][CH2:101][CH2:100][CH2:99][CH2:98]1)=O)=NC(N1CCCCC1)=O.[O:103]1CCCC1>>[CH3:49][C:2](=[CH2:1])[C:3]([O:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][O:17][C:18](=[O:48])[C:19]1[CH:24]=[C:23]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][O:31][O:32][C:33]2[CH:38]=[CH:37][C:36](/[CH:39]=[CH:40]/[C:41]([O:43][CH3:44])=[O:42])=[CH:35][C:34]=2[O:45][CH3:46])[CH:102]=[CH:101][C:100]=1[CH2:99][CH2:98][CH2:84][CH2:83][CH2:82][CH2:81][O:103][O:51][C:52](=[O:71])/[CH:53]=[CH:54]/[C:55]1[CH:60]=[CH:59][C:58]([O:61][CH2:62][CH2:63][CH2:64][CH3:65])=[C:57]([O:69][CH3:70])[CH:56]=1)=[O:4]

Participants

6

Reactant 5

HCID 8028Tetrahydrofuran2×HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 541470624-(6-Hydroxyhexyloxy)-3-methoxycinnamic acid methyl esterHCID 86759259(E)-2-hydroxy-5-[6-[2-methoxy-4-(methoxycarbonylvinyl)phenoxy]oxyhexyl]benzoic acid 11-(2-methylacryloyloxy)undecyl ester

Product 1

HCID 88055413(E,E)-5-[6-[2-methoxy-4-(methoxycarbonylvinyl)phenoxy]oxyhexyl]-2-[6-[3-(3-methoxy-4-butoxyphenyl)acryloyloxy]oxyhexyl]benzoic acid 11-(2-methylacryloyloxy)undecyl esterYield 62%

Procedure

0.81 g (1.18 mmol) (E)-2-hydroxy-5-[6-[2-methoxy-4-(methoxycarbonylvinyl)phenoxy]oxyhexyl]benzoic acid 11-(2-methylacryloyloxy)undecyl ester, 0.414 g (1.18 mmol) 4-(6-hydroxyhexyloxy)-3-methoxycinnamic acid methyl ester and 0.31 ml (1.24 mmol) of tributylphosphine were dissolved in 10 ml of tetrahydrofuran to which a mixture of 0.313 g (1.24 mmol) of 1,1′-(azodicarbonyl)dipiperidine and 5 ml tetrahydrofuran was subsequently added in a dropwise fashion over a period of 1 hour. The mixture was allowed to react for 18 hours at room temperature. The reaction mixture was then partitioned between ethyl acetate and water, the organic phase was washed with repeatedly with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated by evaporation. Chromatography of the crude product on 120 g of silica gel using toluene:ethyl acetate 4:1 and crystallisation form tert-butyl methyl ether yielded 0.63 g (62%) (E,E)-5-[6-[2-methoxy-4-(methoxycarbonylvinyl)phenoxy]oxyhexyl]-2-[6-[3-(3-methoxy-4-butoxyphenyl)acryloyloxy]oxyhexyl]benzoic acid 11-(2-methylacryloyloxy)undecyl ester as white crystals.

Workup

  1. additionwas subsequently added in a dropwise fashion over a period of 1 hour
  2. customto react for 18 hours at room temperature
  3. customThe reaction mixture was then partitioned between ethyl acetate and water
  4. washthe organic phase was washed with repeatedly with saturated sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated by evaporation
  8. customtoluene:ethyl acetate 4:1 and crystallisation
  9. customform tert-butyl methyl ether

Sources & evidence

ORD record
ord-60f44e1d8ab940718d81321c5d02a457
Source dataset
uspto-grants-2004_12
Patent number
US06833421B1

Reaction notes

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