Triethylamine → methyl (1S,3R)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-[2-(6-chloro-2-fluoro-3-methoxy-phenyl)acetyl]-1-methyl-3,4-dihydro-1H-isoquinoline-5-carboxylate

HRID 1854588Notes

Reaction equation

HRID 1854588 reaction equation
C(N(CC)CC)C.[Si:8]([O:15][CH2:16][C@H:17]1[CH2:26][C:25]2[C:24]([C:27]([O:29][CH3:30])=[O:28])=[CH:23][CH:22]=[CH:21][C:20]=2[C@H:19]([CH3:31])[NH:18]1)([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:10])[CH3:9].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1.[Cl:65][C:66]1[C:71]([CH2:72][C:73](O)=[O:74])=[C:70]([F:76])[C:69]([O:77][CH3:78])=[CH:68][CH:67]=1.[Cl-].[NH4+]>CN(C)C=O>[Si:8]([O:15][CH2:16][C@H:17]1[CH2:26][C:25]2[C:24]([C:27]([O:29][CH3:30])=[O:28])=[CH:23][CH:22]=[CH:21][C:20]=2[C@H:19]([CH3:31])[N:18]1[C:73](=[O:74])[CH2:72][C:71]1[C:66]([Cl:65])=[CH:67][CH:68]=[C:69]([O:77][CH3:78])[C:70]=1[F:76])([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:9])[CH3:10]

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 2724699PyBOPHCID 467375092-(6-Chloro-2-fluoro-3-methoxyphenyl)acetic acidHCID 123884369methyl (1S,3R)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-methyl-1,2,3,4-tetrahydroisoquinoline-5-carboxylate

Product 1

HCID 123499849methyl (1S,3R)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-[2-(6-chloro-2-fluoro-3-methoxy-phenyl)acetyl]-1-methyl-3,4-dihydro-1H-isoquinoline-5-carboxylateYield 89.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add triethylamine (0.36 mL, 2.57 mmol) to a stirred solution of methyl (1S,3R)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-methyl-1,2,3,4-tetrahydroisoquinoline-5-carboxylate (500 mg, 1.29 mmol), (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (1.02 g, 1.93 mmol) and 2-(6-chloro-2-fluoro-3-methoxy-phenyl)acetic acid (356 mg, 1.54 mmol) in dimethylformamide (6.4 mL). Stir at room temperature for 16 h. Add saturated aqueous ammonium chloride (60 mL). Extract with ethyl acetate (3×50 mL). Wash the combined organic layers with brine. Dry over magnesium sulfate, filter and concentrate under reduced pressure. Purify by flash chromatography to yield the title compound as an amorphous yellow solid (703 mg, 1.15 mmol): MS (m/z): 550.0 (M+1).

Workup

  1. extractionExtract with ethyl acetate (3×50 mL)
  2. washWash the combined organic layers with brine
  3. dry with materialDry over magnesium sulfate
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. customPurify by flash chromatography

Sources & evidence

ORD record
ord-034535f778ac4272ba483033ef74c1d8
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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