Diisopropylethylamine → 8-(2-Ethoxy-4-ethoxycarbonylmethyl-phenyl)-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid 4-fluoro-benzyl ester

HRID 1774014Notes

Reaction equation

HRID 1774014 reaction equation
[CH2:1]([O:3][C:4](=[O:26])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][C:15]([F:22])=[C:16]3[C:21]=2[CH2:20][NH:19][CH2:18][CH2:17]3)=[C:8]([O:23][CH2:24][CH3:25])[CH:7]=1)[CH3:2].C(N(C(C)C)C(C)C)C.[F:36][C:37]1[CH:54]=[CH:53][C:40]([CH2:41][O:42][C:43](=O)[O:44]N2C(=O)CCC2=O)=[CH:39][CH:38]=1>C(Cl)Cl.C([O-])(O)=O.[Na+]>[F:36][C:37]1[CH:38]=[CH:39][C:40]([CH2:41][O:42][C:43]([N:19]2[CH2:18][CH2:17][C:16]3[C:21](=[C:12]([C:9]4[CH:10]=[CH:11][C:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:26])=[CH:7][C:8]=4[O:23][CH2:24][CH3:25])[CH:13]=[CH:14][C:15]=3[F:22])[CH2:20]2)=[O:44])=[CH:53][CH:54]=1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 857843262,5-Dioxo-1-pyrrolidinyl (4-fluorophenyl)methyl carbonateHCID 89648851[3-Ethoxy-4-(5-fluoro-1,2,3,4-tetrahydro-isoquinolin-8-yl)-phenyl]-acetic acid ethyl ester

Product 1

HCID 1183531708-(2-Ethoxy-4-ethoxycarbonylmethyl-phenyl)-5-fluoro-3,4-dihydro-1H-isoquinoline-2-carboxylic acid 4-fluoro-benzyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of [3-ethoxy-4-(5-fluoro-1,2,3,4-tetrahydro-isoquinolin-8-yl)-phenyl]-acetic acid ethyl ester (1.49 g, 4.2 mmol, 1.00 eq.) and N-ethyldiisopropylamine (3.56 mL, 20.8 mmol, 5.00 eq.) in DCM (50 mL), carbonic acid 2,5-dioxo-pyrrolidin-1-yl ester 4-fluoro-benzyl ester (1.17 g, 4.4 mmol, 1.05 eq.) was added. The mixture was stirred at r.t. for 18 hours. The solution was diluted with sat. aq. NaHCO3 soln. (100 mL). The layers were separated. The aq. phase was extracted with DCM (2×). The comb. org. phases were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 100 fractions of 45 mL, Heptane 100% to Heptane+40% AcOEt) to yield the title compound as a colorless oil.

Workup

  1. customThe layers were separated
  2. extractionThe aq. phase was extracted with DCM (2×)
  3. dry with materialphases were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flashmaster (column: 100 g, flow: 45 mL/min, 100 fractions of 45 mL, Heptane 100% to Heptane+40% AcOEt)

Sources & evidence

ORD record
ord-5c5c4266d6fc454ba8574adbc0af2cc2
Source dataset
uspto-grants-2016_02
Patent number
US09255090B2

Reaction notes

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