Acetic Acid → HCID 66863034, compound

HRID 1669913Notes

Reaction equation

HRID 1669913 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH:21]=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([Cl:32])[C:25]=1[CH3:33].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CN(C=O)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([O:13][Si:14]([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15])[C@H:9]1[CH2:21][NH:23][C:24]1[CH:31]=[CH:30][C:27]([C:28]#[N:29])=[C:26]([Cl:32])[C:25]=1[CH3:33])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 16731848(2S,3S)-tert-Butyl 3-((tert-butyldimethylsilyl)oxy)-2-formylpyrrolidine-1-carboxylateHCID 218754134-Amino-2-chloro-3-methylbenzonitrile

Product 1

HCID 66863034HCID 66863034, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 7B (730 mg, 2.21 mmol) in 10% DMF in CH2Cl2 (5.5 mL) at rt was added 4-amino-2-chloro-3-methyl-benzonitrile (400 mg, 2.4 mmol) followed acetic acid (200 μL) and sodium triacetoxyborohydride (730 mg, 3.5 mmol). The reaction was stirred for 24 h at rt. The reaction was then extracted with EtOAc and washed with saturated aqueous NaHCO3. The organic extracts were dried over MgSO4 filtered and concentrated. Purification by flash chromatography (silica gel, 0-20% EtOAc in hexanes) provided impure (2R,3S)—N-tert-Butyloxycarbonyl-3-(tert-butyldimethylsilanyloxy)-2-[(3-chloro-4-cyano-2-methyl-phenylamino)-methyl]pyrrolidine as a light brown residue. This residue was taken up in 10% TFA in CH2Cl2 (20 mL) and stirred for 2.5 h at rt. Toluene (10 mL) was added and solvents were removed under vacuum. Purification by preparative HPLC (separated into 4 injections, YMC C18 5 μm 30×100 mm, 0-100% B, 10 min grad., 2 min. hold, 25 mL/min.: A=10% MeOH/Water+0.1% TFA, B=90% MeOH/Water+0.1% TFA) provided the title compound (267 mg). MS (ES) m/z 380.23 [M+1]+

Workup

  1. extractionThe reaction was then extracted with EtOAc
  2. washwashed with saturated aqueous NaHCO3
  3. dry with materialThe organic extracts were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography (silica gel, 0-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f574e798d7ed4c38a40cc7714dee8931
Source dataset
uspto-grants-2011_08
Patent number
US07989640B2

Reaction notes

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