Acetyl chloride → HCID 71656215, compound

HRID 2278244Notes

Reaction equation

HRID 2278244 reaction equation
[NH2:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:8]=2[CH2:9][N:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][CH:19]([C:24]([F:27])([F:26])[F:25])[C:20]([F:23])([F:22])[F:21])=[O:17])[CH2:12][CH2:11]2)[CH2:3]1.CCN(C(C)C)C(C)C.[C:42](Cl)(=[O:44])[CH3:43]>C(Cl)Cl>[C:42]([NH:1][C@@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:31]=[C:30]([Cl:32])[CH:29]=[CH:28][C:8]=2[CH2:9][N:10]2[CH2:11][CH2:12][N:13]([C:16]([O:18][CH:19]([C:24]([F:27])([F:26])[F:25])[C:20]([F:21])([F:22])[F:23])=[O:17])[CH2:14][CH2:15]2)[CH2:3]1)(=[O:44])[CH3:43]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 89682762HCID 89682762, compound

Product 1

HCID 71656215HCID 71656215, compoundYield 99.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A 4 mL vial was charged with (R)-1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(3-aminopyrrolidin-1-yl)-4-chlorobenzyl)piperazine-1-carboxylate (28 mg, 0.057 mmol), a magnetic stirbar, CH2Cl2 (2 mL), and DIPEA (30 μL, 0.172 mmol). The reaction was cooled to 0° C. and an acetyl chloride solution (7 mg, 0.086 mmol, in 1 mL CH2Cl2) was added dropwise. After stirring for 30 min at 0° C., the reaction was quenched with sat Na2CO3 and extracted with CH2Cl2 (3×). The organics were dried (Na2SO4), filtered, and concentrated. The residue was chromatographed on a silica gel column (100% to 10% MeOH in CH2Cl2) and yielded (R)-1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(3-acetamidopyrrolidin-1-yl)-4-chlorobenzyl)piperazine-1-carboxylate (30 mg, 35%). 1H NMR 400 MHz (CDCl3) δ 7.31 (d, J=8.2 Hz, 1H), 6.91 (dd, J=8.1, 1.8 Hz, 1H), 6.86 (d, J=1.9 Hz, 1H), 5.84-5.70 (m, 2H), 4.62-4.50 (m, 1H), 3.59-3.53 (m, 4H), 3.50 (s, 2H), 3.48-3.44 (m, 1H), 3.43-3.33 (m, 1H), 3.20-3.10 (m, 2H), 2.50-2.42 (m, 4H), 2.34 (td, J=13.4, 7.6 Hz, 1H), 2.01 (s, 3H), 1.91-1.79 (m, 1H). LCMS (ESI, m/z): 531 [M+H]+.

Workup

  1. customthe reaction was quenched with sat Na2CO3
  2. extractionextracted with CH2Cl2 (3×)
  3. dry with materialThe organics were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was chromatographed on a silica gel column (100% to 10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-56eca4b53a1e4e45a50892c11a1b3713
Source dataset
uspto-grants-2015_09
Patent number
US09133148B2

Reaction notes

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