Diisopropylethylamine → tert-butyl 1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate

HRID 2202212Notes

Reaction equation

HRID 2202212 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([F:13])[C:8]=1[Si:9]([CH3:12])([CH3:11])[CH3:10])[NH2:5].[C:14]([O:18][C:19]([N:21]1[CH2:30][CH2:29][C:28]2[C:23](=[CH:24][CH:25]=[C:26]([O:31][CH3:32])[CH:27]=2)[CH:22]1[C:33](O)=[O:34])=[O:20])([CH3:17])([CH3:16])[CH3:15].CCN(C(C)C)C(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC>CN(C1C=CN=CC=1)C.C(OCC)(=O)C.O>[F:1][C:2]1[CH:3]=[C:4]([NH:5][C:33]([CH:22]2[C:23]3[C:28](=[CH:27][C:26]([O:31][CH3:32])=[CH:25][CH:24]=3)[CH2:29][CH2:30][N:21]2[C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])=[O:34])[CH:6]=[C:7]([F:13])[C:8]=1[Si:9]([CH3:10])([CH3:12])[CH3:11]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 206007132-(Tert-butoxycarbonyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acidHCID 1254649723,5-Difluoro-4-(trimethylsilyl)aniline

Product 1

HCID 131735725tert-butyl 1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylateYield 58.3%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3,5-difluoro-4-(trimethylsilyl)aniline (700 mg, 3.48 mmol), 2-(tert-butoxycarbonyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (1176 mg, 3.83 mmol), DMAP (467 mg, 3.83 mmol) and DIEA (3.04 mL, 17.39 mmol) in ethyl acetate (6.0 mL) was added T3P (6.14 mL, 10.43 mmol) at room temperature, and the mixture was stirred at 80° C. for 2 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The precipitate was washed with diethyl ether/hexane to give tert-butyl 1-((3,5-difluoro-4-(trimethylsilyl)phenyl)carbamoyl)-6-methoxy-3,4-dihydroisoquinoline-2(1H)-carboxylate (994.1 mg, 2.026 mmol, 58.3%) as white crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. washThe precipitate was washed with diethyl ether/hexane

Sources & evidence

ORD record
ord-27dae646ec214e53840cfe801578cf03
Source dataset
uspto-grants-2016_06
Patent number
US09365520B2

Reaction notes

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