Acetic Anhydride → HCID 66672800, compound

HRID 422859Notes

Reaction equation

HRID 422859 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[CH2:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]2([CH2:19][O:18][C:17]3[CH:20]=[C:21]4[C:25](=[CH:26][C:16]2=3)[CH2:24][CH2:23][O:22]4)[C:8]1=[O:27].[C:28](OC(=O)C)(=[O:30])[CH3:29].C(N(CC)CC)C>ClCCl.Cl>[C:28]([N:1]1[CH2:5][CH2:4][CH2:3][C@H:2]1[CH2:6][N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]2([CH2:19][O:18][C:17]3[CH:20]=[C:21]4[C:25](=[CH:26][C:16]2=3)[CH2:24][CH2:23][O:22]4)[C:8]1=[O:27])(=[O:30])[CH3:29]

Participants

6

Reactant 3

HCID 7918Acetic AnhydrideHCID 8471TriethylamineHCID 59352434HCID 59352434, compound

Product 1

HCID 66672800HCID 66672800, compoundYield 84%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 1′-[(2S)-pyrrolidin-2-ylmethyl]-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.23 g, 0.62 mmol), acetic anhydride (0.09 mL, 0.95 mmol) and triethylamine (0.17 mL, 1.2 mmol) in dichloromethane (4 mL) was stirred at ambient temperature for 40 min. The reaction was diluted with 0.2 M hydrochloric acid (50 mL) and extracted with dichloromethane (3×25 mL). The combined organic solution was dried over sodium sulfate, filtered and concentrated under reduced pressure. Purification by flash column chromatography with dichloromethane/diethyl ether (4:1) afforded 1′-{[(2S)-1-acetylpyrrolidin-2-yl]methyl}-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one (0.21 g, 84%) as an off-white solid: mp 103-108° C. (hexanes); 1H NMR (300 MHz, CDCl3) (diastereomers) δ 7.54, 7.53 (d, J=7.8 Hz, 1H), 7.35, 7.34 (dd, J=8.1, 7.7 Hz, 1H), 7.15 (d, J=7.5 Hz, 1H), 7.06 (dd, J=7.5 Hz, 1H), 6.49, 6.46 (s, 1H), 6.42, 6.41 (s, 1H), 4.91, 4.90 (d, J=9.0 Hz, 1H), 4.68, 4.67 (d, J=9.0 Hz, 1H), 4.54, 4.53 (t, J=8.7 Hz, 2H), 4.49-4.42 (m, 1H), 3.95-3.80 (m, 2H), 3.61-3.54 (m, 1H), 3.46-3.36 (m, 1H), 3.00, 2.99 (t, J=8.6 Hz, 2H), 2.26-1.76 (m, 4H), 2.11-2.08 (s, 3H); 13C NMR (75 MHz, CDCl3) (diastereomers) δ 178.49, 178.47, 170.2, 161.9, 161.8, 161.5, 161.4, 142.6, 142.4, 132.5, 132.3, 129.36, 129.33, 123.8, 123.7, 123.6, 123.5, 120.4, 120.2, 120.0, 119.9, 119.2, 118.7, 110.01, 109.96, 93.4, 93.2, 80.9, 80.8, 72.5, 57.9, 55.0, 54.8, 47.9, 41.5, 41.2, 29.2, 29.1, 28.0, 27.8, 23.9, 22.92, 22.90; MS (ES+) m/z 405.1 (M+1).

Workup

  1. extractionextracted with dichloromethane (3×25 mL)
  2. dry with materialThe combined organic solution was dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography with dichloromethane/diethyl ether (4:1)

Sources & evidence

ORD record
ord-e38dbda87f1c40939264421b0edfe02a
Source dataset
uspto-grants-2012_01
Patent number
US08101647B2

Reaction notes

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