Phthalimide, N-(2-formylethyl)- → HCID 86629526, compound

HRID 1711163Notes

Reaction equation

HRID 1711163 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH2:20][C:21]2[CH:25]=[CH:24][S:23][CH:22]=2)[C:15]([NH:17][O:18][CH3:19])=[O:16])[CH2:10][CH2:9]1)=O)(C)(C)C.C(OC(N1CCC(NCC2C=CSC=2)CC1)=O)(C)(C)C.[O:46]=[C:47]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[C:49](=[O:56])[N:48]1[CH2:57][CH2:58]C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.C(O)(C(F)(F)F)=O.C(O)(=O)C>[O:46]=[C:47]1[C:55]2[C:50](=[CH:51][CH:52]=[CH:53][CH:54]=2)[C:49](=[O:56])[N:48]1[CH2:57][CH2:58][CH2:6][N:8]1[CH2:9][CH2:10][CH:11]([N:14]([CH2:20][C:21]2[CH:25]=[CH:24][S:23][CH:22]=2)[C:15]([NH:17][O:18][CH3:19])=[O:16])[CH2:12][CH2:13]1

Participants

8

Reactant 4

HCID 75525Phthalimide, N-(2-formylethyl)-HCID 5049666Sodium triacetoxyborohydrideHCID 63248157HCID 63248157, compoundHCID 86629525HCID 86629525, compound

Product 1

HCID 86629526HCID 86629526, compoundYield 62%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6344DichloromethaneSolvent2×HCID 6422Trifluoroacetic acidSolvent

Procedure

4-(3-Methoxy-1-thiophen-3-ylmethyl-ureido)-piperidine-1-carboxylic acid tert-butyl ester (0.950 g, 2.69 mmol) was dissolved in a 3:1 mixture of CH2Cl2 and TFA and the mixture was stirred at rt for 1 h. The solvent was removed in vacuo and the resulting brown oil pumped in vacuo (high vacuum system) for 2 h. Using general procedure A, the crude amine, 3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propionaldehyde (0.561 g, 2.75 mmol), acetic acid (20 drops, cat.) and sodium triacetoxyborohydride (0.792 g, 3.75 mmol) were combined in CH2Cl2 (40 ml) and the resulting mixture was stirred at rt for 16 h. Standard basic workup gave the crude product as a tan oil. Purification by column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 94:5:1, v/v/v) gave 1-{1-[3-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-propyl]-piperidin-4-yl}-3-methoxy-1-thiophen-3-ylmethyl-urea as a white foam (0.692 g, 62%). 1H NMR (CDCl3) δ 1.36 (m, 2H), 1.59 (m, 2H), 1.85 (p, 2H, J=4.5 Hz), 1.91 (t, 2H, J=9.0 Hz), 2.39 (t, 2H, J=6.0 Hz), 2.88 (d, 2H, J=12.0 Hz), 3.62 (s, 3H), 3.75 (t, 2H, J=6.0 Hz), 4.04 (s, 2H), 4.23 (m, 1H), 6.90 (d, 1H, J=3.0 Hz), 6.99 (s, 1H), 7.06 (s, 1H), 7.36 (m, 1H), 7.62 (m, 2H), 7.81 (m, 2H).

Workup

  1. customThe solvent was removed in vacuo
  2. waitthe resulting brown oil pumped in vacuo (high vacuum system) for 2 h
  3. stirringthe resulting mixture was stirred at rt for 16 h
  4. customStandard basic workup gave the crude product as a tan oil
  5. customPurification by column chromatography on silica gel (CH2Cl2:MeOH:NH4OH, 94:5:1, v/v/v)

Sources & evidence

ORD record
ord-e6de8a2b9cc74ff2a00ee47a44d71135
Source dataset
uspto-grants-2010_09
Patent number
US07790747B2

Reaction notes

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