Acetyl chloride → HCID 73891112, compound

HRID 2278690Notes

Reaction equation

HRID 2278690 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C@@H:13]([CH3:14])[C@H:12]([CH2:15][C:16]([O:18]C)=[O:17])[N:11]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH:27]4[CH2:32][CH2:31][N:30]([C:33]5[CH:38]=[C:37]([O:39][CH2:40][CH3:41])[CH:36]=[CH:35][C:34]=5[F:42])[CH2:29][CH2:28]4)=[CH:22][CH:21]=3)[N:10]=2)=[CH:5][CH:4]=1)#[N:2].C(C[C@@H]1N(C2C=CC(OC3CCN(C4C=C(OCC)C=CC=4F)CC3)=CC=2)N=C(C2C=CC(C#N)=CC=2)[C@H]1C)#N.COC(C)=O.C(Cl)(C)=O>Cl.CO.C(Cl)Cl.CO.C(Cl)Cl>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C@@H:13]([CH3:14])[C@H:12]([CH2:15][C:16]([OH:18])=[O:17])[N:11]([C:20]3[CH:21]=[CH:22][C:23]([O:26][CH:27]4[CH2:28][CH2:29][N:30]([C:33]5[CH:38]=[C:37]([O:39][CH2:40][CH3:41])[CH:36]=[CH:35][C:34]=5[F:42])[CH2:31][CH2:32]4)=[CH:24][CH:25]=3)[N:10]=2)=[CH:5][CH:4]=1)#[N:2]

Participants

8

Reactant 4

HCID 6367Acetyl chlorideHCID 6584Methyl AcetateHCID 86719428HCID 86719428, compoundHCID 86719431Methyl 2-((4S,5S)-3-(4-cyanophenyl)-1-(4-((1-(5-ethoxy-2-fluorophenyl)piperidin-4-yl)oxy)phenyl)-4-methyl-4,5-dihydro-1H-pyrazol-5-yl)acetate

Product 1

HCID 73891112HCID 73891112, compoundYield 18%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 21226129Dichloromethane methanolSolventHCID 21893726Hydrochloride methanolSolvent

Procedure

Methyl 2-((4S,5S)-3-(4-cyanophenyl)-1-(4-((1-(5-ethoxy-2-fluorophenyl)piperidin-4-yl)oxy)phenyl)-4-methyl-4,5-dihydro-1H-pyrazol-5-yl)acetate: 4-((4S,5S)-5-(Cyanomethyl)-1-(4-((1-(5-ethoxy-2-fluorophenyl)piperidin-4-yl)oxy)phenyl)-4-methyl-4,5-dihydro-1H-pyrazol-3-yl)benzonitrile (389 mg, 0.716 mmol) was dissolved in ˜2.5M HCl/MeOH, MeOAc, CH2Cl2 solution [36.6 mL, prepared by addition of AcCl (6.6 mL) to 3/2 CH2Cl2/MeOH (30.0 mL) at 0° C. and then stirring at rt for 30 min]. The resulting solution was stirred at rt for 6.5 h and then evaporated to a volume of about 5 mL. The oily remnant was stripped from MeOH (2×20 mL), taken up in EtOAc (100 mL) and, washed with 5% NaHCO3 (2×50 mL) and sat'd NaCl (40 mL). The organic layer was dried (Na2SO4) and concentrated. Purification via silica gel chromatography provided the desired (75 mg, 18% yield) as a yellow oil: LC-MS [M+H] 571.

Workup

  1. stirringThe resulting solution was stirred at rt for 6.5 h
  2. customevaporated to a volume of about 5 mL
  3. washwashed with 5% NaHCO3 (2×50 mL) and sat'd NaCl (40 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. concentrationconcentrated
  6. customPurification via silica gel chromatography
  7. customprovided the

Sources & evidence

ORD record
ord-3425615993f94d6fb19d1075db5f1cc7
Source dataset
uspto-grants-2015_09
Patent number
US09133163B2

Reaction notes

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