Acetic Acid → 3-[2-(Benzofuran-2-ylmethoxycarbonylamino)-2-(1-phenyl-ethylcarbamoyl)-propyl]-indole-1-carboxylic acid 4-morpholin-4-ylmethyl-benzoyloxymethyl ester monohydrochloride salt

HRID 1384506Notes

Reaction equation

HRID 1384506 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(O)(=O)C.[CH:11]([C:13]1[CH:62]=[CH:61][C:16]([C:17]([O:19][CH2:20][O:21][C:22]([N:24]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:26]([CH2:33][C:34]([NH:47][C:48]([O:50][CH2:51][C:52]3[O:53][C:54]4[CH:60]=[CH:59][CH:58]=[CH:57][C:55]=4[CH:56]=3)=[O:49])([C:36](=[O:46])[NH:37][CH:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH3:39])[CH3:35])=[CH:25]2)=[O:23])=[O:18])=[CH:15][CH:14]=1)=O.C(=O)(O)[O-].[Na+].[Cl:68]CCl>>[ClH:68].[N:1]1([CH2:11][C:13]2[CH:62]=[CH:61][C:16]([C:17]([O:19][CH2:20][O:21][C:22]([N:24]3[C:32]4[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=4)[C:26]([CH2:33][C:34]([NH:47][C:48]([O:50][CH2:51][C:52]4[O:53][C:54]5[CH:60]=[CH:59][CH:58]=[CH:57][C:55]=5[CH:56]=4)=[O:49])([C:36](=[O:46])[NH:37][CH:38]([C:40]4[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=4)[CH3:39])[CH3:35])=[CH:25]3)=[O:23])=[O:18])=[CH:15][CH:14]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

6

Reactant 5

HCID 176Acetic AcidHCID 6344DichloromethaneHCID 8083MorpholineHCID 516892Sodium BicarbonateHCID 206699173-[2-(Benzofuran-2-ylmethoxycarbonylamino)-2-(1-phenyl-ethylcarbamoyl)-propyl]-indole-1-carboxylic acid 4-formylbenzoyloxymethyl ester

Product 1

HCID 702045543-[2-(Benzofuran-2-ylmethoxycarbonylamino)-2-(1-phenyl-ethylcarbamoyl)-propyl]-indole-1-carboxylic acid 4-morpholin-4-ylmethyl-benzoyloxymethyl ester monohydrochloride saltYield 70%

Procedure

Morpholine (0.164 mL, 1.88 mmol, 1.1 eq.) and acetic acid (0.108 mL, 1.88 mmol, 1.1 eq.) were added to a solution of compound 19 (1.2 g, 1.71 mmol) in dry dichloromethane (20 mL) under N2 in an ice bath. Then NaHB(OAC)3 (0.508 g, 2.39 mmol, 1.4 eq.) was added in three equal portions in 10 minutes. After the addition, the reaction mixture was stirred for 3 hours at room temperature. A solution of saturated sodium bicarbonate (30 mL) was added to the reaction mixture and stirred at room temperature for 30 minutes. The organic layer was separated and washed sequentially with a solution of saturated sodium bicarbonate (20 mL), a solution of saturated sodium chloride, and dried over anhydrous sodium sulfate. The solvent was evaporated, and the residue was purified by silica gel chromatography eluting with CHCl3/MeOH (10:0.1) to give compound 20b as a white foam (0.921 g, 70%).

Workup

  1. addition(0.508 g, 2.39 mmol, 1.4 eq.) was added in three equal portions in 10 minutes
  2. additionAfter the addition
  3. stirringstirred at room temperature for 30 minutes
  4. customThe organic layer was separated
  5. washwashed sequentially with a solution of saturated sodium bicarbonate (20 mL)
  6. dry with materiala solution of saturated sodium chloride, and dried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customthe residue was purified by silica gel chromatography
  9. washeluting with CHCl3/MeOH (10:0.1)

Sources & evidence

ORD record
ord-2d5a4072a17844acb08bf90d0b9652d1
Source dataset
uspto-grants-2001_07
Patent number
US06258800B1

Reaction notes

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