Acetic Anhydride → HCID 66852222, compound

HRID 876354Notes

Reaction equation

HRID 876354 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([OH:16])[CH2:13][CH:12]1[CH2:17][C:18]1[C:26]2[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=2)[NH:20][CH:19]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:28](OC(=O)C)(=[O:30])[CH3:29]>CN(C1C=CN=CC=1)C.C(Cl)Cl>[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH:14]([O:16][C:28](=[O:30])[CH3:29])[CH2:13][CH:12]1[CH2:17][C:18]1[C:26]2[C:21](=[CH:22][C:23]([F:27])=[CH:24][CH:25]=2)[NH:20][CH:19]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 7918Acetic AnhydrideHCID 66851381HCID 66851381, compound

Product 1

HCID 66852222HCID 66852222, compoundYield 63%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution containing 7 (4.7 g, 12.8 mmol) and DMAP (81 mg, 0.66 mmol) in DCM (100 mL) was added acetic anhydride (2.6 g, 25.5 mmol) at ambient temperature. After 16 h, the reaction mixture was quenched with a MeOH (ca. 3 mL) and washed successively with 10% aq. Na2CO3 (50 mL), dilute HCl (50 mL), and 10% aq. Na2CO3 (50 mL). The organic solution was concentrated in vacuo and filtered through a short column of silica gel (ca. 25 g) [eluant: DCM (200 mL) to 0.5% (v/v) MeOH/DCM (80 mL) to 2% MeOH/DCM (100 mL) to 5% MeOH/DCM (100 mL)]. The product-containing fractions were combined and concentrated to provide 3.28 g (63%) of 8 as a white foam [Note: 94.3 A % by HPLC analysis]. 1H NMR (300 MHz, CDCl3), ˜1:1 mixture of rotomers: δ7.99 (m, 1H), 7.75-6.61 (m, 9H), 5.28 (m, 1H), 5.20 (m, 2H), 4.23 (m, 1H), 3.82 (dt, J=5.4, 13.5 Hz, 1H), 3.60 (app. t, J=13.2 Hz, 1H), 3.50 (d, J=11.7 Hz, 0.5H), 3.31 (d, J=12.9 Hz, 0.5H), 2.87 (dt, J=5.1, 13.5 Hz, 1H), 2.13 (s, 3H), 2.01 (m, 2H) ppm; 13C NMR (75 MHz, CDCl3), ˜1:1 mixture of rotomers: δ170.8, 160.2 (JCF=236.4 Hz), 155.2, 136.8, 136.6, 136.4, 128.9, 128.8, 128.5 (JCF=24.3 Hz), 124.5 (JCF=21.4 Hz), 123.0, 123.0, 120.0 (JCF=27.1 Hz), 119.9 (JCF=26.0 Hz), 112.8 (JCF=10.5 Hz), 108.2 (JCF=24.3 Hz), 97.7 (JCF=25.7 Hz), 74.0, 73.2, 67.9, 67.2, 58.5, 57.6, 53.4, 53.0, 35.4, 34.6, 30.8, 29.7, 21.5 ppm. Mass spectrum (ESI), m/z 410.6 [(M)+; calcd for C23H23FN2O4: 410.4].

Workup

  1. customthe reaction mixture was quenched with a MeOH (ca. 3 mL)
  2. washwashed successively with 10% aq. Na2CO3 (50 mL), dilute HCl (50 mL), and 10% aq. Na2CO3 (50 mL)
  3. concentrationThe organic solution was concentrated in vacuo
  4. filtrationfiltered through a short column of silica gel (ca. 25 g) [eluant: DCM (200 mL) to 0.5% (v/v) MeOH/DCM (80 mL) to 2% MeOH/DCM (100 mL) to 5% MeOH/DCM (100 mL)]
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-46ad11bab68c424aa2940026b767b8a0
Source dataset
uspto-grants-2015_03
Patent number
US08986993B2

Reaction notes

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