1,1,3,3-Tetramethylguanidine → 2-benzyloxycarbonylamino-3-[1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indol-5-yl]-acrylic acid methyl ester

HRID 1353508Notes

Reaction equation

HRID 1353508 reaction equation
CN(C)C(N(C)C)=N.[CH3:9][O:10][C:11]([CH:13](P(OC)(OC)=O)[NH:14][C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])=[O:12].[CH3:31][Si:32]([CH3:50])([CH3:49])[CH2:33][CH2:34][S:35]([N:38]1[C:46]2[C:41](=[CH:42][C:43]([CH:47]=O)=[CH:44][CH:45]=2)[CH:40]=[CH:39]1)(=[O:37])=[O:36]>O1CCCC1>[CH3:9][O:10][C:11](=[O:12])[C:13]([NH:14][C:15]([O:17][CH2:18][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)=[O:16])=[CH:47][C:43]1[CH:42]=[C:41]2[C:46](=[CH:45][CH:44]=1)[N:38]([S:35]([CH2:34][CH2:33][Si:32]([CH3:31])([CH3:50])[CH3:49])(=[O:36])=[O:37])[CH:39]=[CH:40]2

Participants

5

Reactant 3

HCID 664601,1,3,3-TetramethylguanidineHCID 2734718Methyl 2-{[(benzyloxy)carbonyl]amino}-2-(dimethyl phosphono)acetateHCID 211020581-(2-Trimethylsilanyl-ethanesulfonyl)-1H-indole-5-carbaldehyde

Product 1

HCID 684643132-benzyloxycarbonylamino-3-[1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indol-5-yl]-acrylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1,1,3,3-Tetramethylguanidine (0.68 mL, 5.43 mmol) was added at room temperature to a solution of N-(benzyloxycarbonyl)-α-phophonoglycine trimethyl ester (1.88 g, 5.69 mmol) in tetrahydrofuran (40 mL). The mixture was stirred at room temperature for 15 min and cooled to −78° C., and a solution of 1-(2-trimethylsilanyl-ethanesulfonyl)-1H-indole-5-carbaldehyde (1.6 g, 5.17 mmol) in tetrahydrofuran (15 mL) was added slowly. The resulting reaction mixture was stirred at −78° C. for 2 h and then warmed to room temperature in 3 h. Solvents were removed in vacuo and the residue was subjected to flash chromatography on silica gel using methylene chloride/hexanes (1:1.5) with 1% triethylamine as eluent to afford the title compound as a 92:8 Z/E mixture (determined by integration of CO2CH3, for Z isomer at 3.79 ppm, and E isomer at 3.65 ppm). For the Z isomer: 1H-NMR (CD3CN, 500 MHz) δ 7.96 (s, 1H), 7.91 (d, J=8.5 Hz, 1H), 7.66 (d, J=8.5 Hz, 1H), 7.56 (d, J=3.7 Hz, 1H), 7.51 (s, 1H), 7.43–7.35 (m, 5H), 7.67 (d, J=3.7 Hz, 1H), 5.16 (s, 2H), 3.79 (s, 3H), 3.42–3.38 (m, 2H), 0.87–0.83 (m, 2H), −0.04 (s, 9H). Mass spec. 515.20 (MH)+.

Workup

  1. temperaturecooled to −78° C.
  2. customThe resulting reaction mixture
  3. stirringwas stirred at −78° C. for 2 h
  4. temperaturewarmed to room temperature in 3 h
  5. customSolvents were removed in vacuo

Sources & evidence

ORD record
ord-8d67c7d216f54b7b880ed8be7a047827
Source dataset
uspto-grants-2007_05
Patent number
US07220862B2

Reaction notes

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