Hydrochloric Acid → Methyl 5-{2-[((2R)-2-{[(benzyloxy)carbonyl]amino}-3-hydroxypropyl)oxy]phenyl}-6-cyclohexyl-3-methyl-4H-thieno[3,2-b]pyrrole-2-carboxylate

HRID 1008997Notes

Reaction equation

HRID 1008997 reaction equation
[CH:1]1([C:7]2[C:8]3[S:24][C:23]([C:25]([O:27][CH3:28])=[O:26])=[C:22]([CH3:29])[C:9]=3[N:10](COC)[C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[OH:18])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.CC1(C)[N:36]([C:37]([O:39][CH2:40][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)=[O:38])[C@@H:35]([CH2:47]OS(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)[CH2:34][O:33]1>O1CCOCC1.CN(C=O)C.CO>[CH2:40]([O:39][C:37]([NH:36][C@H:35]([CH2:34][OH:33])[CH2:47][O:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:11]1[NH:10][C:9]2[C:22]([CH3:29])=[C:23]([C:25]([O:27][CH3:28])=[O:26])[S:24][C:8]=2[C:7]=1[CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)=[O:38])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

Participants

7

Reactant 3

HCID 313Hydrochloric Acid2×HCID 67298636methyl 6-cyclohexyl-5-(2-hydroxyphenyl)-4-(methoxymethyl)-3-methyl-4H-thieno[3,2-b]pyrrole-2-carboxylateHCID 86629786Phenylmethyl (4R)-2,2-dimethyl-4-((((4-nitrophenyl)sulfonyl)oxy)methyl)-3-oxazolidinecarboxylate

Product 1

HCID 67298563Methyl 5-{2-[((2R)-2-{[(benzyloxy)carbonyl]amino}-3-hydroxypropyl)oxy]phenyl}-6-cyclohexyl-3-methyl-4H-thieno[3,2-b]pyrrole-2-carboxylateYield 31%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

Methyl 6-cyclohexyl-5-(2-hydroxyphenyl)-4-(methoxymethyl)-3-methyl-4H-thieno[3,2-b]pyrrole-2-carboxylate was dissolved in dioxane (0.036M) and the same volume of 6N HCl was added. The mixture was subjected to microwave irradiation (10 min @ 130° C.). All volatiles were evaporated and the product was enriched by prep. RP-HPLC. The product-containing fractions were lyophilised to give a green glassy solid. This material was dissolved in DMF (0.16M) and benzyl (4R)-2,2-dimethyl-4-({[(4-nitrophenyl)sulfonyl]oxy}methyl)-1,3-oxazolidine-3-carboxylate (excess, prepared according to Synthesis 1996, 189 in analogy to benzyl (4R)-2,2-dimethyl-4-({[(4-methylphenyl)sulfonyl]oxy}methyl)-1,3-oxazolidine-3-carboxylate from benzyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate and substituting tosyl chloride with 4-nitrobenzenesulfonyl chloride) was added. The suspension was heated to 50° C. overnight. All volatiles were evaporated i. vac. and the residual material was purified by prep. RP-HPLC. The product fractions were evaporated and the residual material lyophilised from MeCN/water. A beige solid was obtained, which was dissolved dry MeOH (0.2M) and 1.25M HCl in MeOH (excess) was added. The solution was left stirring at RT. After 3 h all volatiles were evaporated and the residual material was subjected to purification by chromatography (PE:EtOAc, 6:4). After evaporation of the product fractions the product was obtained as a yellow powder (31%). MS (ES+) m/z 577 (M+H)+.

Workup

  1. customThe mixture was subjected to microwave irradiation (10 min @ 130° C.)
  2. customAll volatiles were evaporated
  3. customto give a green glassy solid
  4. customAll volatiles were evaporated i
  5. customand the residual material was purified by prep
  6. customThe product fractions were evaporated
  7. customA beige solid was obtained
  8. additionwas added
  9. waitThe solution was left
  10. customAfter 3 h all volatiles were evaporated
  11. customthe residual material was subjected to purification by chromatography (PE:EtOAc, 6:4)
  12. customAfter evaporation of the product fractions the product

Sources & evidence

ORD record
ord-57c851e8c5af467fb6fc9654578a1401
Source dataset
uspto-grants-2011_07
Patent number
US07973026B2

Reaction notes

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