Water → (7R,8aS)-2-[(3-tert-butyl-4-methoxyphenyl)sulfonyl]-7-[(5-cyclopropyl-pyrazin-2-yl)oxy]octahydropyrrolo[1,2-a]pyrazine

HRID 240438Notes

Reaction equation

HRID 240438 reaction equation
[CH:1]1([C:4]2[N:5]=[CH:6][C:7]([O:10][C@H:11]3[CH2:19][N:14]4[CH2:15][CH2:16][NH:17][CH2:18][C@@H:13]4[CH2:12]3)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[C:20]([C:24]1[CH:25]=[C:26]([S:32](Cl)(=[O:34])=[O:33])[CH:27]=[CH:28][C:29]=1[O:30][CH3:31])([CH3:23])([CH3:22])[CH3:21].C(N(C(C)C)CC)(C)C.O>ClCCl>[C:20]([C:24]1[CH:25]=[C:26]([S:32]([N:17]2[CH2:16][CH2:15][N:14]3[CH2:19][C@H:11]([O:10][C:7]4[CH:6]=[N:5][C:4]([CH:1]5[CH2:3][CH2:2]5)=[CH:9][N:8]=4)[CH2:12][C@H:13]3[CH2:18]2)(=[O:34])=[O:33])[CH:27]=[CH:28][C:29]=1[O:30][CH3:31])([CH3:23])([CH3:21])[CH3:22]

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 110652633-tert-Butyl-4-methoxy-benzenesulfonyl chlorideHCID 86680449(7R,8aS)-7-[(5-cyclopropylpyrazin-2-yl)oxy]octahydropyrrolo[1,2-a]pyrazine

Product 1

HCID 71544608(7R,8aS)-2-[(3-tert-butyl-4-methoxyphenyl)sulfonyl]-7-[(5-cyclopropyl-pyrazin-2-yl)oxy]octahydropyrrolo[1,2-a]pyrazine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the product from Example 27B (30 mg, 0.115 mmol) in dichloromethane (1 mL) was added 3-tert-butyl-4-methoxybenzene-1-sulfonyl chloride (36 mg, 0.138 mmol) and diisopropylethylamine (0.040 mL, 0.23 mmol). The resulting mixture was stirred at room temperature for 90 minutes. Water (2 mL) was added, and the mixture was extracted with dichloromethane (2×2 mL). The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to give a crude product. Purification by column chromatography on silica gel eluting with a solvent gradient of 0-60% ethyl acetate in hexanes gave the titled compound. 1H NMR (300 MHz, CDCl3) δ ppm 0.87-1.00 (m, 4H), 1.38 (s, 9H), 1.73-1.87 (m, 1H), 1.91-2.03 (m, 2H), 2.08 (t, J=10.51 Hz, 1H), 2.31 (dd, J=10.17, 5.09 Hz, 1H), 2.37-2.48 (m, 2H), 2.48-2.60 (m, 1H), 2.91-3.05 (m, 1H), 3.63 (dd, J=10.17, 6.78 Hz, 1H), 3.68-3.76 (m, 1H), 3.83-3.90 (m, 1H), 3.90 (s, 3H), 5.23-5.35 (m, 1H), 6.94 (d, J=9.16 Hz, 1H), 7.57-7.66 (m, 2H), 7.91 (d, J=1.36 Hz, 1H), 8.02 (d, J=1.70 Hz, 1H); MS (ESI) m/z 487.1 (M+H)+.

Workup

  1. extractionthe mixture was extracted with dichloromethane (2×2 mL)
  2. dry with materialThe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto give a crude product
  6. customPurification by column chromatography on silica gel eluting with a solvent gradient of 0-60% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-806ccaae526a4b27a380eef9af8b93d8
Source dataset
uspto-grants-2014_02
Patent number
US08648074B2

Reaction notes

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