Trimethyl orthoformate → HCID 67519476, compound

HRID 1925190Notes

Reaction equation

HRID 1925190 reaction equation
[CH:1]1[C:13]2[CH:12]([CH2:14][O:15][C:16](=[O:33])[NH:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]3[CH:30]=[CH:29][C:28](C=O)=[CH:27][CH:26]=3)[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH:46]([O:51][CH3:52])([O:49][CH3:50])OC>CO>[CH:10]1[C:11]2[CH:12]([CH2:14][O:15][C:16](=[O:33])[NH:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[C:25]3[CH:26]=[CH:27][C:28]([CH:46]([O:49][CH3:50])[O:51][CH3:52])=[CH:29][CH:30]=3)[C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 9005Trimethyl orthoformateHCID 521998p-Toluenesulfonic acid monohydrateHCID 86589748HCID 86589748, compound

Product 1

HCID 67519476HCID 67519476, compoundYield 93.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a vigorously stirred mixture of methanol (250 mL) containing aldehyde (S29) (17.0 g, 39.3 mmol) and p-toluenesulfonic acid monohydrate (0.75 g, 3.9 mmol) was added trimethyl orthoformate (17 mL, 160 mmol). After 1.5 h of moderate heating (flask equipped with short path to drive reaction forward), the reaction was quenched with a 1:1 mixture of saturated sodium bicarbonate and water (150 mL) and diluted with CH2Cl2 (200 mL). The aqueous layer was extracted with CH2Cl2 and the combined organic layers were washed with brine, dried over Na2SO4, and concentrated in vacuo to give a pale yellow solid (17.5 g, 36.6 mmol, 93%) which was used without further purification. 1H NMR (400 MHz, d6-DMSO): δ 7.88 (d, 2H, J=7.7 Hz), 7.79 (t, 1H, J=5.9 Hz), 7.68 (d, 2H, J=7.3 Hz), 7.43-7.30 (m, 11H), 7.19 (d, 1H, J=7.0 Hz), 5.40 (s, 1H), 4.29 (d, 2H, J=7.0 Hz), 4.20 (t, 1H, J=7.0 Hz), 4.11 (d, 2H, J=5.9 Hz), 3.25 (s, 6H). FAB/MS: 502 (M+Na+).

Workup

  1. temperatureAfter 1.5 h of moderate heating
  2. custom(flask equipped with short path to drive reaction forward)
  3. customthe reaction was quenched with a 1:1 mixture of saturated sodium bicarbonate and water (150 mL)
  4. additiondiluted with CH2Cl2 (200 mL)
  5. extractionThe aqueous layer was extracted with CH2Cl2
  6. washthe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-df3048d2d3b04e57ba695bc516a08b62
Source dataset
uspto-grants-2012_05
Patent number
US08178579B2

Reaction notes

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