Chlorotrimethylsilane → HCID 58904527, compound

HRID 1292743Notes

Reaction equation

HRID 1292743 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1)[O:6][C@@H:7]([C@:11]1([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13][NH:12]1)[C:8]([OH:10])=[O:9].C1COCC1.Cl[Si](C)(C)C.[C:42]1([CH2:48][C:49](Cl)=[O:50])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>C(Cl)Cl.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1)[O:6][C@@H:7]([C@:11]1([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13][N:12]1[C:49](=[O:50])[CH2:48][C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:8]([OH:10])=[O:9]

Participants

7

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 7679Phenylacetyl chlorideHCID 8028TetrahydrofuranHCID 58904496HCID 58904496, compound

Product 1

HCID 58904527HCID 58904527, compoundYield 46.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of (±)-(S*)-(3,5-dimethoxy-phenoxy)-((1S*)-1-phenyl-1,2,3,4-tetrahydro-isoquinolin-1-yl)-acetic acid (60 mg, 0.143 mmol, Example 1) in THF (5 ml) Hünig's base (122 μl, 0.715 mmol) followed by chlorotrimethylsilane (22 μl, 0.172 mmol) is added at 5° C. The mixture is stirred at 55° C. for 3 h before phenylacetylchloride (29 μl, 0.215 mmol) is added. Stirring is continued at rt for 2 h before water (approx. 200 μl) is added. The mixture is diluted with DCM, washed twice with 2 N aq. HCl. The organic phase is dried over Na2SO4 and evaporated. The crude product is purified by prep. HPLC on Rp-C18 silica gel to give (±)-(S*)-(3,5-dimethoxy-phenoxy)-((1S*)-1-phenyl-2-phenylacetyl-1,2,3,4-tetrahydro-isoquinolin-1-yl)-acetic acid (36 mg) as a white powder. LC-MS1: tR=0.98 min, [M+1]+=538.13.

Workup

  1. additionis added at 5° C
  2. additionis added
  3. additionis added
  4. washwashed twice with 2 N aq. HCl
  5. dry with materialThe organic phase is dried over Na2SO4
  6. customevaporated
  7. customThe crude product is purified by prep

Sources & evidence

ORD record
ord-e12947ae1454497f949c8253dcf8130e
Source dataset
uspto-grants-2007_07
Patent number
US07238685B2

Reaction notes

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