Diiodomethane → (R)-4-(Cyclopropylmethyl)-5-(quinolin-8-ylsulfonyl)-3,4,5,6-tetrahydro-1H-benzo[f][1,4]oxazocine

HRID 1429386Notes

Reaction equation

HRID 1429386 reaction equation
[CH2:1]([C@H:4]1[N:11]([S:12]([C:15]2[CH:16]=[CH:17][CH:18]=[C:19]3[C:24]=2[N:23]=[CH:22][CH:21]=[CH:20]3)(=[O:14])=[O:13])[CH2:10][C:9]2[CH:25]=[CH:26][CH:27]=[CH:28][C:8]=2[CH2:7][O:6][CH2:5]1)[CH:2]=[CH2:3].[CH2:29]([Zn]CC)C.ICI.[Cl-].[NH4+]>C1COCC1>[CH:2]1([CH2:1][C@H:4]2[N:11]([S:12]([C:15]3[CH:16]=[CH:17][CH:18]=[C:19]4[C:24]=3[N:23]=[CH:22][CH:21]=[CH:20]4)(=[O:14])=[O:13])[CH2:10][C:9]3[CH:25]=[CH:26][CH:27]=[CH:28][C:8]=3[CH2:7][O:6][CH2:5]2)[CH2:29][CH2:3]1

Participants

6

Reactant 4

HCID 6346DiiodomethaneHCID 25517Ammonium ChlorideHCID 86677162(R)-4-Allyl-5-(quinolin-8-ylsulfonyl)-3,4,5,6-tetrahydro-1H-benzo[f][1,4]oxazocineHCID 178418750HCID 178418750, compound

Product 1

HCID 71269531(R)-4-(Cyclopropylmethyl)-5-(quinolin-8-ylsulfonyl)-3,4,5,6-tetrahydro-1H-benzo[f][1,4]oxazocineYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of compound 18 (100 mg, 0.25 mmol) in dry THF (5 mL) was added diethyl zinc (1M solution in hexane, 2.5 mL) at 0° C. under nitrogen atmosphere followed by diiodomethane (667 mg, 2.5 mmol). The reaction was stirred at 0° C. for 6 h and poured over cold aqueous solution of ammonium chloride. The organic layer was separated and the aqueous layer extracted repeatedly with EA. The combined organic layer was washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by Prep-TLC to afford the compound 20 (32 mg, 31% yield). 1H NMR (500 MHz, CDCl3) δ 8.94 (m, 1H), 8.47 (d, J=7.5 Hz, 1H), 8.13 (d, J=8.0 Hz, 1H), 7.93 (d, J=8.5 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.43 (dd, J=8.0 Hz, 4.0 Hz 1H), 7.17 (d, J=7.5 Hz, 1H), 6.98 (t, J=7.5 Hz, 1H), 6.89 (m, 1H), 6.80 (d, J=7.5 Hz, 1H), 5.07 (d, J=15.5 Hz, 1H), 4.95 (d, J=15.0 Hz, 1H), 4.86 (d, J=15.5 Hz, 1H), 4.60 (d, J=15.0 Hz, 1H), 4.49 (m, 1H), 4.14 (d, J=12.0 Hz, 1H), 3.75 (d, J=12.0 Hz, 1H), 1.71 (m, 1H), 1.10 (m, 1H), 0.63 (m, 1H), 0.33 (m, 2H), −0.11 (m, 2H). MS (ESI+) m/z: 409 [M+H]+. LCMS (m/z): 409.2 (MH+).

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer extracted repeatedly with EA
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by Prep-TLC

Sources & evidence

ORD record
ord-7dfe3f3a592946c49df6a7c2cc53e22e
Source dataset
uspto-grants-2015_01
Patent number
US08940722B2

Reaction notes

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