1-Hydroxybenzotriazole → 3-[4-(N-BOC-Piperidin-4-yl)butyloxy]isoxazole-5-carbonyl-2(S)-phenylsulfonylamino-beta-alanine methyl ester

HRID 1957583Notes

Reaction equation

HRID 1957583 reaction equation
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][CH2:16][CH2:17][O:18][C:19]2[CH:23]=[C:22]([C:24]([OH:26])=O)[O:21][N:20]=2)[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.[C:28]1([S:34]([NH:37][C@@H:38]([CH2:43][NH2:44])[C:39]([O:41][CH3:42])=[O:40])(=[O:36])=[O:35])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>C(Cl)CCl.CN(C=O)C>[CH3:42][O:41][C:39](=[O:40])[C@@H:38]([NH:37][S:34]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)(=[O:36])=[O:35])[CH2:43][NH:44][C:24]([C:22]1[O:21][N:20]=[C:19]([O:18][CH2:17][CH2:16][CH2:15][CH2:14][CH:11]2[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]2)[CH:23]=1)=[O:26]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 190681503-[4-(N-BOC-Piperidin-4-yl)butyloxy]isoxazole-5-carboxylic acidHCID 22865877Methyl 3-Amino-2(S)-phenylsulfonylaminopropionate hydrochloride

Product 1

HCID 867529453-[4-(N-BOC-Piperidin-4-yl)butyloxy]isoxazole-5-carbonyl-2(S)-phenylsulfonylamino-beta-alanine methyl esterYield 72.3%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6228DimethylformamideSolvent

Procedure

A stirred mixture of 4-5 (147 mg, 0.4 mmol), 2-9a (149 mg, 0.4 mmol), HOBT (61 mg, 0.4 mmol), DIEA (215 μL, 1.2 mmol), and DMF (6 mL) at -15° C. was treated with EDC (77 mg, 0.4 mL) followed by removal of the cooling bath. After 72 h, the reaction mixture was diluted with EtOAc and then washed with 1M NaHSO4 and brine, dried (MgSO4), and concentrated. Flash chromatography (silica, 10% acetone/CH2Cl2) gave 4-6 (176 mg) as a viscous oil. Rf 0.24 (silica, 10% acetone/CH2Cl2).

Workup

  1. customfollowed by removal of the cooling bath
  2. additionthe reaction mixture was diluted with EtOAc
  3. washwashed with 1M NaHSO4 and brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-c675be25555043648775db5039eeaa6b
Source dataset
uspto-grants-1998_07
Patent number
US05786373

Reaction notes

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