Acetic Acid → 4-{[1-(4-Iodophenyl)cyclopropyl]methyl}morpholine

HRID 1521821Notes

Reaction equation

HRID 1521821 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:11]=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1.[BH3-]C#N.[Na+].C(O)(=O)C>ClCCCl>[I:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2([CH2:11][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH2:9][CH2:10]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8083MorpholineHCID 5003444Sodium cyanoborohydrideHCID 582563541-(4-Iodophenyl)cyclopropanecarbaldehyde

Product 1

HCID 665797454-{[1-(4-Iodophenyl)cyclopropyl]methyl}morpholine

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 1-(4-iodophenyl)cyclopropanecarbaldehyde (7 g, 0.025 mol) in 1,2-Dichloroethane (100 mL) is added morpholine (4.5 mL, 0.051 mol) in drops at 0° C. . After 10 min, NaBH3CN (3.2 g, 30 mmol) is added in a portion wise fashion at 0° C. followed by acetic acid (500 μL). The reaction mixture is stirred for another 1 h at same temperature and then at Rt for 10 h. After this time, the reaction mixture is quenched with 10% sodium bicarbonate and extracted with EtOAc. The combined organic layer is washed with water, brine, dried over sodium sulphate and evaporated. The crude product is purified by column chromatography (pet ether and EtOAc) to afford the title compound as colourless liquid. 1H NMR (DMSO-d6, 400 MHz) δ 7.60-7.56 (m, 2H), 7.13-7.08 (m, 2H), 3.47-3.43 (m, 4H), 2.50-2.46 (m, 2H), 2.34 (bs, 4H) 0.0.80-0.77 (m, 2H),0.72-00.69 (m, 2H).

Workup

  1. waitat Rt for 10 h
  2. customAfter this time, the reaction mixture is quenched with 10% sodium bicarbonate
  3. extractionextracted with EtOAc
  4. washThe combined organic layer is washed with water, brine
  5. dry with materialdried over sodium sulphate
  6. customevaporated
  7. customThe crude product is purified by column chromatography (pet ether and EtOAc)

Sources & evidence

ORD record
ord-a0cb062dd85a4b39b2a4da411e4c78d3
Source dataset
uspto-grants-2015_07
Patent number
US09073940B2

Reaction notes

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