Azobisisobutyronitrile → HCID 21180691, compound

HRID 1386794Notes

Reaction equation

HRID 1386794 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14](O)[C:15]([F:22])([F:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(=O)C(OC)=O.C[Si]([SiH]([Si](C)(C)C)[Si](C)(C)C)(C)C.N(C(C)(C)C#N)=NC(C)(C)C#N>CN(C1C=CN=CC=1)C.C(Cl)Cl.C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([CH2:14][C:15]([F:22])([F:21])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 4

HCID 6547AzobisisobutyronitrileHCID 79846Methyl chloroglyoxylateHCID 123134Tris(trimethylsilyl)silaneHCID 21180610HCID 21180610, compound

Product 1

HCID 21180691HCID 21180691, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2.25 g (6.7 mmol) of ethyl 3-(1-(t-butoxycarbonyl)-piperidin-4-yl)-3-hydroxy-2,2-difluoropropionate (from EXAMPLE 176, Step A) and 2.50 g (20.5 mmol) of 4-(N,N-dimethylamino)pyridine in 40 mL of CH2Cl2 at 0° C. was treated with 1.10 mL (12.0 mmol) of methyl chlorooxoacetate. The resulting mixture was warmed to rt, stirred for 1 h, then quenched with 100 mL of 0.5 N KHSO4. The quenched mixture was extracted with 250 mL of EtOAc; the extract was dried and concentrated. The crude oxalate ester, 3.70 mL (12.0 mmol) of tris(trimethylsilyl)silane and 500 mg (3.0 mmol) of 2,2′-azobisisobutyronitrile in 20 mL of toluene was heated at reflux under an Ar atmosphere for 1.5 h. The reaction mixture was cooled and concentrated. Flash chromatography on 75 g of silica gel using 10:1 v/v, then 4:1 v/v hexanes/ether as the eluants afforded 922 mg (43%) of the title compound as an oil: 1H NMR (500 MHz, CDCl3) δ 1.16-1.25 (m, 2H), 1.36 (t, J=7.0, 31), 1.46 (s, 9H), 1.74 (app d, J=15.0, 2H), 1.75-1.81 (m, 1H), 2.02 (dt, J=6.0, 18.0,22H), 2.68-2.73 (m, 2H), 4.05-4.09 (m, 2H), 4.33 (q, J=7.0, 2H).

Workup

  1. customquenched with 100 mL of 0.5 N KHSO4
  2. extractionThe quenched mixture was extracted with 250 mL of EtOAc
  3. customthe extract was dried
  4. concentrationconcentrated
  5. temperatureat reflux under an Ar atmosphere for 1.5 h
  6. temperatureThe reaction mixture was cooled
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-de799d695de14a3fb89c3ecdbcd006c4
Source dataset
uspto-grants-2001_07
Patent number
US06265434B1

Reaction notes

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