Methyl 1-(((1 (R)-(3-formylphenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropaneacetate → Methyl 1-(((1(R)-(3-(2-(3-bromothieno[3,2-b]pyridin-5-yl)-ethenyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropaneacetate

HRID 2259498Notes

Reaction equation

HRID 2259498 reaction equation
CC(C)([O-])C.[K+].[Cl-].[Br:8][C:9]1[C:13]2=[N:14][C:15]([CH2:18][P+](C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)=[CH:16][CH:17]=[C:12]2[S:11][CH:10]=1.[CH:38]([C:40]1[CH:41]=[C:42]([C@H:46]([S:59][CH2:60][C:61]2([CH2:64][C:65]([O:67][CH3:68])=[O:66])[CH2:63][CH2:62]2)[CH2:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=2[C:55]([OH:58])([CH3:57])[CH3:56])[CH:43]=[CH:44][CH:45]=1)=O>C1COCC1>[Br:8][C:9]1[C:13]2=[N:14][C:15]([CH:18]=[CH:38][C:40]3[CH:41]=[C:42]([C@H:46]([S:59][CH2:60][C:61]4([CH2:64][C:65]([O:67][CH3:68])=[O:66])[CH2:62][CH2:63]4)[CH2:47][CH2:48][C:49]4[CH:54]=[CH:53][CH:52]=[CH:51][C:50]=4[C:55]([OH:58])([CH3:57])[CH3:56])[CH:43]=[CH:44][CH:45]=3)=[CH:16][CH:17]=[C:12]2[S:11][CH:10]=1

Participants

5

Reactant 3

HCID 22857739Methyl 1-(((1 (R)-(3-formylphenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropaneacetateHCID 23665647Potassium tert-butoxideHCID 88252588((3-Bromothieno[3,2-b]pyridin-5-yl)methyl)triphenylphosphonium chloride

Product 1

HCID 54048065Methyl 1-(((1(R)-(3-(2-(3-bromothieno[3,2-b]pyridin-5-yl)-ethenyl)phenyl)-3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropaneacetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 1 molar solution of potassium t-butoxide (0.57 mL, 0.57 mmol) was added to a -78° C. suspension of the phosphonium salt (0.290 g, 0.55 mmol) of Step 4, in 3 mL of THF. The temperature was brought to 0° C. for 20 min then lowered back to -78° C. followed by the addition of a 0.5 molar solution of methyl 1-(((1(R)-(3-formylphenyl)3-(2-(1-hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropaneacetate (1.47 mL, 0.44 mmol) of Step 17 of Example 1. The bath was brought to 0° C. for 1 hr and the reaction mixture was quenched with a 25% aqueous NH4OAc. The organic solvents were evaporated and the title product was purified by flash chromatography on silica with EtOAc:hexane 30:70 to yield 0.270 g (94%).

Workup

  1. customthen lowered back to -78° C.
  2. waitThe bath was brought to 0° C. for 1 hr
  3. customthe reaction mixture was quenched with a 25% aqueous NH4OAc
  4. customThe organic solvents were evaporated
  5. customthe title product was purified by flash chromatography on silica with EtOAc:hexane 30:70
  6. customto yield 0.270 g (94%)

Sources & evidence

ORD record
ord-b25a7cfbdcb9420585c314b3648709a4
Source dataset
uspto-grants-1995_12
Patent number
US05472964

Reaction notes

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