Acetic Acid → 4-(5-Cyclopropylamino-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalene-2-ylethynyl)-benzoic acid ethyl ester

HRID 1069834Notes

Reaction equation

HRID 1069834 reaction equation
[CH2:1]([O:3][C:4](=[O:26])[C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:22]=[CH:21][C:20]3[C:19](=O)[CH2:18][CH2:17][C:16]([CH3:25])([CH3:24])[C:15]=3[CH:14]=2)=[CH:7][CH:6]=1)[CH3:2].[CH:27]1([NH2:30])[CH2:29][CH2:28]1.C(O)(=O)C.C([BH3-])#N.[Na+]>ClCCl.C(#N)C.O.C(=O)([O-])[O-].[Na+].[Na+]>[CH2:1]([O:3][C:4](=[O:26])[C:5]1[CH:6]=[CH:7][C:8]([C:11]#[C:12][C:13]2[CH:22]=[CH:21][C:20]3[CH:19]([NH:30][CH:27]4[CH2:29][CH2:28]4)[CH2:18][CH2:17][C:16]([CH3:25])([CH3:24])[C:15]=3[CH:14]=2)=[CH:9][CH:10]=1)[CH3:2]

Participants

9

Reactant 4

HCID 176Acetic AcidHCID 69828CyclopropylamineHCID 5003444Sodium cyanoborohydrideHCID 15345545Ethyl 4-[(5,6,7,8-tetrahydro-8,8-dimethyl-5-oxonaphth-2-yl)ethynyl]benzoate2×

Product 1

HCID 129717084-(5-Cyclopropylamino-8,8-dimethyl-5,6,7,8-tetrahydro-naphthalene-2-ylethynyl)-benzoic acid ethyl esterYield 64.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

A solution of 4-(8,8-dimethyl-5-oxo-5,6,7,8-tetrahydro-naphthalene-2-ylethynyl)-benzoic acid ethyl ester (Intermediate 14, 0.14 g, 0.4 mmol) in 3 mL of dichloromethane and 2 mL of acetonitrile was treated with cyclopropyl amine (1 mL, 14.45 mmol). After 5 minutes, acetic acid (1 mL) was added followed by sodium cyanoborohydride (0.13 g, 2 mmol). The reaction was stirred overnight at ambient temperature. It was then diluted with water and saturated aqueous sodium carbonate solution and extracted with dichloromethane (×2). The combined organic extract was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to an oil. Flash column chromatography over silica gel (230-400 mesh) using 20% ethyl acetate in hexane as the eluent afforded the title compound (0.1 g, 62%) as a pale yellow solid. 1H-NMR (300 MHz, CDCl3): δ 0.30-0.60(m, 4H), 1.28(s, 3H), 1.35 (s, 3H), 1.30(t, J=7.1 Hz, 3H), 1.55-1.61(m, 1H), 1.83-2.05(m, 3H), 2.25 (quintet, J=3.0 Hz, 1H), 3.80 (t, J=4.9 Hz, 1H), 4.39(q, J=7.1 Hz, 2H), 7.27-7.36(m, 2H), 7.52 (s, 1H), 7.55(d, J=8.3 Hz, 2H), 8.03(d, J=8.5 Hz, 2H).

Workup

  1. extractionextracted with dichloromethane (×2)
  2. extractionThe combined organic extract
  3. dry with materialwas dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo to an oil

Sources & evidence

ORD record
ord-2a0e588a3857496a920a44e18c965fb0
Source dataset
uspto-grants-2001_06
Patent number
US06252090B1

Reaction notes

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