Diisopropylethylamine → HCID 68284010, compound

HRID 1527415Notes

Reaction equation

HRID 1527415 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[C@@H:10]([OH:14])[C@H:9]1[C:15]([OH:17])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:18][C:19]1[C:20]([F:27])=[C:21]([CH:24]=[CH:25][CH:26]=1)[CH2:22][NH2:23].CCCP(=O)=O.CCN(C(C)C)C(C)C>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([F:13])[C@@H:10]([OH:14])[C@H:9]1[C:15](=[O:17])[NH:23][CH2:22][C:21]1[CH:24]=[CH:25][CH:26]=[C:19]([Cl:18])[C:20]=1[F:27])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2773614(3-Chloro-2-fluorophenyl)methanamineHCID 16167369Propylphosphoric anhydrideHCID 68283661HCID 68283661, compound

Product 1

HCID 68284010HCID 68284010, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (2S,3S,4S)-4-fluoro-3-hydroxy-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester (195 g, 0.782 mmol) in CH2Cl2 (10 mL) were added 3-chloro-2-fluoro-benzylamine (150 mg, 0.94 mmol), propylphosphonic anhydride (50% in EtOAc, 0.346 mL, 1.17 mmol) and DIPEA (0.41 mL, 2.35 mmol). The reaction mixture was stirred 1 h at RT, then quenched by addition of a saturated aqueous solution of NaHCO3 and extracted with CH2Cl2 (×2). The combined organic extracts were dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 1:1). MS (UPLC): 391.3/393.1 [M+H]+, 435.4/437.4 [M+HCOO]−; tR (HPLC conditions f): 1.95 min.

Workup

  1. customquenched by addition of a saturated aqueous solution of NaHCO3
  2. extractionextracted with CH2Cl2 (×2)
  3. dry with materialThe combined organic extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash column chromatography on silica gel (c-hexane/EtOAc 1:1)
  7. custom1.95 min.

Sources & evidence

ORD record
ord-e8bf1d9f4b4942538bc9a59add9aabe0
Source dataset
uspto-grants-2015_07
Patent number
US09085555B2

Reaction notes

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