Diisopropylamine → (S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-5-phenyl-pentanoic acid methyl ester

HRID 1455568Notes

Reaction equation

HRID 1455568 reaction equation
Cl.[CH3:2][O:3][C:4](=[O:18])[C@@H:5]([NH2:17])[CH2:6][C:7]([F:16])([F:15])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(NC(C)C)(C)C.[N:26]1([C:32](Cl)=[O:33])[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1>ClCCl.O>[CH3:2][O:3][C:4](=[O:18])[C@@H:5]([NH:17][C:32]([N:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1)=[O:33])[CH2:6][C:7]([F:16])([F:15])[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

6

Reactant 3

HCID 7912DiisopropylamineHCID 848104-Morpholinecarbonyl chlorideHCID 68820868(S)-2-amino-4,4-difluoro-5-phenyl-pentanoic acid methyl ester hydrochloride

Product 1

HCID 57535362(S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-5-phenyl-pentanoic acid methyl esterYield 88.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of (S)-2-amino-4,4-difluoro-5-phenyl-pentanoic acid methyl ester hydrochloride (2.50 g, 8.94 mmol) and diisopropyl amine (22.3 mmol, 2.89 g) in dry dichloromethane (40 mL) under N2 is added drop wise morpholine carbonyl chloride (13.4 mmol, 2.0 g). The mixture is stirred at room temperature for 15 hours, and then diluted with water (50 mL). The aqueous layer is extracted with dichloromethane (30 mL). The organic layers are dried over magnesium sulfate and then concentrated in vacuum. Purification over 110 g silica gel, eluting with EtOAc:Heptane (1:1, then 2:1) affords (S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-5-phenyl-pentanoic acid methyl ester (2.82 g, 88.5%).

Workup

  1. extractionThe aqueous layer is extracted with dichloromethane (30 mL)
  2. dry with materialThe organic layers are dried over magnesium sulfate
  3. concentrationconcentrated in vacuum
  4. customPurification over 110 g silica gel
  5. washeluting with EtOAc:Heptane (1:1

Sources & evidence

ORD record
ord-2d5cbf0c018e4446a35ea53c000e8e66
Source dataset
uspto-grants-2009_01
Patent number
US07482448B2

Reaction notes

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