Triethylamine → (S)-1'-[2-t-Butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionyl]spiro[2H-1-benzopyran-2,4'-piperidin]-4-(3H)-one

HRID 1419595Notes

Reaction equation

HRID 1419595 reaction equation
C(N(CC)CC)C.[C:8]([O:12][C:13]([NH:15][C@@H:16]([CH2:20][O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[C:17]([OH:19])=O)=[O:14])([CH3:11])([CH3:10])[CH3:9].Cl.[NH:32]1[CH2:37][CH2:36][C:35]2([CH2:42][C:41](=[O:43])[C:40]3[CH:44]=[CH:45][CH:46]=[CH:47][C:39]=3[O:38]2)[CH2:34][CH2:33]1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>CN(C)C=O.O>[C:8]([O:12][C:13]([NH:15][C@@H:16]([CH2:20][O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[C:25]([Cl:30])[CH:24]=1)[C:17]([N:32]1[CH2:37][CH2:36][C:35]2([CH2:42][C:41](=[O:43])[C:40]3[CH:44]=[CH:45][CH:46]=[CH:47][C:39]=3[O:38]2)[CH2:34][CH2:33]1)=[O:19])=[O:14])([CH3:9])([CH3:10])[CH3:11]

Participants

9

Reactant 6

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2771097Spiro(1-benzopyran-2,4'-piperidin)-4(3H)-one--hydrogen chloride (1/1)HCID 11760269(S)-2-t-butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionic acid

Product 1

HCID 21308496(S)-1'-[2-t-Butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionyl]spiro[2H-1-benzopyran-2,4'-piperidin]-4-(3H)-oneYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Triethylamine (0.50 mL, 0.36 g, 3.6 mmol) was added to a stirred, cooled (0° C.) mixture of (S)-2-t-butoxycarbonylamino-3-(3,4-dichlorobenzyloxy)propionic acid (364 mg, 1 mmol), spiro[2H-1-benzopyran-2,4'-piperidin]-4-(3H)-one hydrochloride (U.S. Pat. No. 5,206,240, Example 67A) (254 mg, 1 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (230 mg, 1.2 mmol) and 1-hydroxybenzotriazole (162 mg, 1.2 mmol) in dimethylformamide (5 mL) and the mixture was stirred at room temperature for 2 h. Aqueous sodium hydrogen carbonate (saturated, 20 mL) and water (10 mL) were added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organic fractions were washed with aqueous citric acid (10%, 2×20 mL), aqueous sodium hydrogen carbonate (saturated, 2×20 mL) and brine (20 mL), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with CH2Cl2 /MeOH (99.5:0.5 increasing to 98:2) to give the title compound as a colorless foam (248 mg, 44%). m/e (ES+) 563 (MH+).

Workup

  1. temperaturecooled
  2. extractionthe mixture was extracted with ethyl acetate (3×20 mL)
  3. washThe combined organic fractions were washed with aqueous citric acid (10%, 2×20 mL), aqueous sodium hydrogen carbonate (saturated, 2×20 mL) and brine (20 mL)
  4. dry with materialdried (MgSO4)
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by flash column chromatography on silica gel
  7. washeluting with CH2Cl2 /MeOH (99.5:0.5 increasing to 98:2)

Sources & evidence

ORD record
ord-7994efdf0a6c4152b303725714307214
Source dataset
uspto-grants-1999_03
Patent number
US05885999

Reaction notes

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