Water → HCID 58748302, compound

HRID 1162712Notes

Reaction equation

HRID 1162712 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([NH:13][C:14]([C:16]2[S:17][C:18]([Cl:21])=[CH:19][CH:20]=2)=[O:15])[CH2:10][C@H:9]1[CH:22]=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[F:24][CH:25]([F:28])[CH2:26][NH2:27].[BH3-]C#N.[Na+].O>C(O)C.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4]>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([NH:13][C:14]([C:16]2[S:17][C:18]([Cl:21])=[CH:19][CH:20]=2)=[O:15])[CH2:10][C@H:9]1[CH2:22][NH:27][CH2:26][CH:25]([F:28])[F:24])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 962WaterHCID 1362742,2-DifluoroethanamineHCID 5003444Sodium cyanoborohydrideHCID 58748281HCID 58748281, compound

Product 1

HCID 58748302HCID 58748302, compoundYield 44.4%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 702EthanolSolvent

Procedure

89.2 A mixture of 200 mg (2S,4R)-4-[(5-chloro-thiophene-2-carbonyl)-amino]-2-formyl-pyrrolidine-1-carboxylic acid tert-butyl ester, 90 mg 2,2-difluorethyl amine (solution in 1 ml THF) and 0.33 ml tetraisopropyl orthotitanate was stirred at r.t. for 1 h 30. The mixture was diluted with 1.5 ml ethanol and 35 mg NaBH3CN was added. Stirring at r.t. was continued for 18 h. Then, 0.5 ml H2O was added and stirring was continued for 30 min. The mixture was concentrated. The crude product was purified by column chromatography (silica gel; gradient: cyclohexane->cyclohexane/EtOAc 3:7) to give 105 mg (2S,4R)-4-[(5-chloro-thiophene-2-carbonyl)-amino]-2-[(2,2-difluoro-ethylamino)-methyl]-pyrrolidine-1-carboxylic acid tert-butyl ester as white amorphous solid. MS 424.0 ([M+H]+)

Workup

  1. additionwas added
  2. stirringStirring at r.t.
  3. waitwas continued for 18 h
  4. stirringstirring
  5. waitwas continued for 30 min
  6. concentrationThe mixture was concentrated
  7. customThe crude product was purified by column chromatography (silica gel; gradient: cyclohexane->cyclohexane/EtOAc 3:7)

Sources & evidence

ORD record
ord-014efa4c09db4489a31ff347142d5993
Source dataset
uspto-grants-2010_10
Patent number
US07820699B2

Reaction notes

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