Diiodomethane → HCID 57723035, compound

HRID 1987154Notes

Reaction equation

HRID 1987154 reaction equation
[CH2:1]([N:5]([CH2:16][CH2:17][CH3:18])[C:6](=[O:15])[O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)/[CH:2]=[CH:3]/[CH3:4].[CH2:19]([Zn]CC)C.ICI>C(Cl)Cl>[CH3:4][CH:3]1[CH2:19][CH:2]1[CH2:1][N:5]([CH2:16][CH2:17][CH3:18])[C:6](=[O:15])[O:7][CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 6346DiiodomethaneHCID 57723102HCID 57723102, compoundHCID 178418750HCID 178418750, compound

Product 1

HCID 57723035HCID 57723035, compoundYield 97.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Cbz Protection A solution of propylamine (9.0 g, 152.4 mmol) and triethylamine (15.4 g, 152.4 mmol) in methylene chloride (350 mL) was cooled to 0° C. and treated with benzyl chloroformate (20.0 g, 117.2 mmol). Upon stirring at 0° C. for 1 hour the reaction was warmed to ambient temperature and quenched with 1N HCl. The reaction was partitioned between 1N HCl and methylene chloride. The organics were washed with 1N HCl, water and brine. The combined organics were dried over sodium sulfate, filtered and evaporated in vacuo to give benzyl propylcarbamate as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.37 (m, 5H), 5.10 (s, 2H), 4.77 (bs, 1H), 3.16 (q, J=6.5 Hz, 2H), 1.52 (m, 2H), 0.92 (t, J=7.5 Hz, 3H). Step B: Alkylation A solution of benzyl propylcarbamate (20.8 g, 107.9 mmol) in DMF (200 mL) was cooled to 0° C. and treated with sodium hydride (4.6 g, 194.2 mmol). The reaction was stirred to 0° C. for 15 minutes and subsequently treated with crotyl bromide (17.5 g, 129.5 mmol). The reaction was warmed to ambient temperature and stirred for 16 hours. The reaction was quenched with ammonium chloride solution and partitioned between water and ether. The organics were washed with water (4×) and brine, dried over sodium sulfate, filtered and evaporated in vacuo. Flash chromatography (silica, 0-10% EtOAc/hexanes) gave benzyl (2E)-but-2-enyl(propyl)carbamate as a clear oil. 1H NMR (400 MHz, CDCl3) δ 7.35 (m, 5H), 5.57 (bt, 1H), 5.42 (bs, 1H), 5.13 (s, 2H), 3.82 (bm, 2H), 3.19 (bs, 2H), 1.68 (bs, 3H), 1.54 (bs, 2H), 0.87 (bs, 3H). Step C: Cyclopropanation A solution of benzyl (2E)-but-2-enyl(propyl)carbamate (5.0 g, 20.2 mmol) in methylene chloride (120 mL) was cooled to 0° C. and treated with diethylzinc (12.48 g, 101 mmol) followed by diiodomethane (54.1 g, 202 mmol). The reaction was warmed to ambient temperature and stirred for 16 hours. The reaction was quenched with saturated ammonium chloride solution and partitioned between methylene chloride and saturated sodium bicarbonate solution. The organics were dried over sodium sulfate, filtered and evaporated in vacuo. Flash chromatography (10% EtOAc/hexanes) gave 5.16 g (96%) of benzyl (2-methylcyclopropyl)methyl(propyl)carbamate as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.35 (m, 5H), 5.13 (s, 2H), 3.16 (bm, 4H), 1.59 (bm, 2H), 1.01 (bs, 3H), 0.88 (bs, 3H), 0.68 (bs, 2H), 0.34 (bd, 1H), 0.22 (bs, 2H). Step D: Hydrogenation

Workup

  1. customThe reaction was quenched with saturated ammonium chloride solution
  2. custompartitioned between methylene chloride and saturated sodium bicarbonate solution
  3. dry with materialThe organics were dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-75e34c77cedb4d54b446114784c9b6e4
Source dataset
uspto-grants-2009_06
Patent number
US07550481B2

Reaction notes

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