Proton sponge → tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-methoxypropoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate

HRID 75749Notes

Reaction equation

HRID 75749 reaction equation
[CH2:1]([C@@H:8]1[C@@H:16]([O:17][CH2:18][CH2:19][CH2:20][OH:21])[C@H:15]([CH3:22])[O:14][C:13](=[O:23])[C@@H:12]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:32]N(C1C2C(N(C)C)=CC=CC=2C=CC=1)C.F[B-](F)(F)F.C[O+](C)C>C(Cl)Cl>[CH2:1]([C@@H:8]1[C@@H:16]([O:17][CH2:18][CH2:19][CH2:20][O:21][CH3:32])[C@H:15]([CH3:22])[O:14][C:13](=[O:23])[C@@H:12]([NH:24][C:25](=[O:31])[O:26][C:27]([CH3:30])([CH3:29])[CH3:28])[CH2:11][O:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 88675Proton spongeHCID 2735153Oxonium, trimethyl-, tetrafluoroborate(1-) (1:1)HCID 86701242tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-hydroxypropoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate

Product 1

HCID 86701241tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-methoxypropoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamateYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-hydroxypropoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate (118 mg, 0.270 mmol, 1.00 equiv) in CH2Cl2 (2.7 mL, 0.1 M) were added Proton Sponge™ (87 mg, 0.41 mmol, 1.5 equiv) and trimethyloxonium tetrafluoroborate (44 mg, 0.30 mmol, 1.1 equiv). A white precipitate quickly formed. The resulting mixture was stirred at room temperature for 16 h, quenched with 1 N HCl (2 mL), diluted with H2O (20 mL), and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated to provide a white solid. Purification by automated silica gel column chromatography (4-30% acetone in hexanes) provided tert-butyl ((3S,7S,8R,9S)-7-benzyl-8-(3-methoxypropoxy)-9-methyl-2-oxo-1,5-dioxonan-3-yl)carbamate (118 mg, 72%) as a colorless oil: IR (ATR) 3347, 2978, 2928, 2875, 1750, 1710, 1496, 1354, 1367, 1385, 1327, 1163, 1088, 910, 855, 731 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.28 (dd, J=8.6, 6.9 Hz, 2H), 7.24-7.14 (m, 3H), 5.13 (d, J=8.1 Hz, 1H), 4.94 (dq, J=9.3, 6.4 Hz, 1H), 4.60 (dd, J=14.9, 7.3 Hz, 1H), 3.88 (dd, J=11.5, 7.3 Hz, 1H), 3.76 (dt, J=12.7, 6.3 Hz, 1H), 3.63 (dt, J=8.7, 6.3 Hz, 1H), 3.53-3.42 (m, 3H), 3.41-3.33 (m, 1H), 3.30 (s, 4H), 3.28-3.22 (m, 1H), 3.18-3.05 (m, 2H), 2.29 (t, J=12.7

Workup

  1. customA white precipitate quickly formed
  2. customquenched with 1 N HCl (2 mL)
  3. additiondiluted with H2O (20 mL)
  4. extractionextracted with CH2Cl2 (3×20 mL)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto provide a white solid
  9. customPurification by automated silica gel column chromatography (4-30% acetone in hexanes)

Sources & evidence

ORD record
ord-cd769b390cf34a4fa9aadba7d002800a
Source dataset
uspto-grants-2014_09
Patent number
US08835462B2

Reaction notes

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