Formaldehyde → HCID 42602360, compound

HRID 1867652Notes

Reaction equation

HRID 1867652 reaction equation
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][O:7][CH2:8][C:9]1([CH2:19][CH2:20]N)[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12][CH2:11][O:10]1.[C:31]([BH3-])#[N:32].[Na+].[CH2:35]=O>C(#N)C>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[CH2:6][O:7][CH2:8][C:9]1([CH2:19][CH2:20][N:32]([CH3:31])[CH3:35])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12][CH2:11][O:10]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 42602280HCID 42602280, compound

Product 1

HCID 42602360HCID 42602360, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-(1-((3,5-bis(trifluoromethyl)benzyloxy)methyl)isochroman-1-yl)ethanamine (25 mg, 0.058 mmol) and sodium cyanoborohydride (18.1 mg, 0.288 mmol) in acetonitrile (1.2 mL) at 0° C. was added formalin (0.15 mL). The ice bath was removed and stirring continued for 1 h, occasionally treating with a small drop of acetic acid to keep the pH slightly less than 7. The reaction was concentrated, dissolved in methanol, and loaded onto an SCX cartridge. The cartridge was flushed with several volumes of methanol which were discarded. The crude product was eluted with 2M ammonia in methanol and concentrated. The product was purified by column chromatography (5%-->10% MeOH/DCM) to give 15 mg (56%) as a colorless film. 1H-NMR (CD3OD, 300 MHz) δ 7.84 (m, 3H), 7.08-7.27 (m, 4H), 4.69 (qAB, JAB=13.1 Hz, 2H), 4.01 (m, 1H), 3.93 (ddd, J=11.3, 5.2, 4.0 Hz, 1H), 3.80 (qAB, JAB=10.4 Hz, 2H), 2.88 (m, 1H), 2.68 (ddd, J=16.2, 3.7, 3.4 Hz, 1H), 2.50 (m, 1H), 2.22 (m, 1H), 2.18 (s, 6H), 2.00-2.12 (m, 2H); 13C-NMR (CD3OD, 126 MHz) δ 142.6, 137.3, 135.3, 131.7 (q, J=32.6 Hz), 129.0, 127.5, 126.9, 126.5, 125.6, 123.8 (q, J=272 Hz), 121.0, 78.3, 76.7, 71.7, 60.7, 54.1, 44.3, 35.2, 29.4. Mass spec.: 462.40 (MH)+. Accurate mass spec.: m/z 462.1882 [MH]+, Δ=3.1 ppm.

Workup

  1. customThe ice bath was removed
  2. additionoccasionally treating with a small drop of acetic acid
  3. concentrationThe reaction was concentrated
  4. dissolutiondissolved in methanol
  5. customThe cartridge was flushed with several volumes of methanol which
  6. washThe crude product was eluted with 2M ammonia in methanol
  7. concentrationconcentrated
  8. customThe product was purified by column chromatography (5%-->10% MeOH/DCM)
  9. customto give 15 mg (56%) as a colorless film

Sources & evidence

ORD record
ord-f5eaea191e844d148cb3968337b43e7b
Source dataset
uspto-grants-2009_12
Patent number
US07632861B2

Reaction notes

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