Ammonium Chloride → HCID 71513606, compound

HRID 1914492Notes

Reaction equation

HRID 1914492 reaction equation
[C:1](Cl)(=[O:29])[O:2][C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C@@H:10]2[C@@H:14]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH3:25])[CH:17]=3)[CH2:13][O:12][C:11]2=[O:26])=[CH:5][C:4]=1[O:27][CH3:28].[NH:31]1[CH2:35][CH2:34][CH2:33][CH2:32]1.[NH4+].[Cl-]>C(Cl)Cl>[N:31]1([C:1]([O:2][C:3]2[CH:8]=[CH:7][C:6]([CH2:9][C@@H:10]3[C@@H:14]([CH2:15][C:16]4[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[C:18]([O:24][CH3:25])[CH:17]=4)[CH2:13][O:12][C:11]3=[O:26])=[CH:5][C:4]=2[O:27][CH3:28])=[O:29])[CH2:35][CH2:34][CH2:33][CH2:32]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 31268PyrrolidineHCID 86676734HCID 86676734, compound

Product 1

HCID 71513606HCID 71513606, compoundYield 45.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To the above solution 4-(((3R,4R)-4-(3,4-dimethoxybenzyl)-2-oxotetrahydrofuran-3-yl)methyl)-2-methoxyphenyl carbonochloridate (124 mg, 0.33 mmol, 1.0 eq) in DCM (15 mL) was added TEA (67 mg, 0.66 mmol, 2.0 eq), followed by pyrrolidine (65 mg, 0.60 mmol, 1.5 eq) at 0° C. The mixture was stirred at rt over 2 days, basified with sat. aq. NH4Cl (30 mL), and extracted with DCM (30 mL×3). The combined organic layers were dried over MgSO4, filtered and concentrated. The resulting residue was purified by prep-HPLC to afford 4-(((3R,4R)-4-(3,4-dimethoxybenzyl)-2-oxotetrahydrofuran-3-yl)methyl)-2-methoxyphenyl pyrrolidine-1-carboxylate (71.0 mg, 45.4% from two steps). LRMS (M+H+) m/z calculated 470.2, found 469.9. 1H NMR (CDCl3, 400 MHz) δ 7.00 (d, 1H), 6.74-6.78 (m, 2H), 6.64-6.70 (m, 1H), 6.50-6.56 (m, 2H), 4.12-4.17 (m, 1H), 3.82-3.90 (m, 1H), 3.85 (s, 3H), 3.83 (s, 3H), 3.77 (s, 3H), 3.56-3.60 (m, 2H), 3.44-3.48 (m, 2H), 2.97 (d, 2H), 2.48-2.68 (m, 4H), 1.90-1.98 (m, 4H).

Workup

  1. extractionextracted with DCM (30 mL×3)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-f5dc71f15dc046cead5e211bdf123705
Source dataset
uspto-grants-2013_12
Patent number
US08614211B2

Reaction notes

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