Formaldehyde → HCID 42602277, compound

HRID 1867642Notes

Reaction equation

HRID 1867642 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:6][O:7][CH2:8][C:9]1([CH2:18][CH2:19]N)[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][O:10]1.[CH2:30]=O.[C:32]([BH3-])#[N:33].[Na+]>C(#N)C>[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([CH:21]=[C:22]([C:24]([F:27])([F:26])[F:25])[CH:23]=1)[CH2:6][O:7][CH2:8][C:9]1([CH2:18][CH2:19][N:33]([CH3:32])[CH3:30])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11][O:10]1

Participants

5

Reactant 3

HCID 712FormaldehydeHCID 5003444Sodium cyanoborohydrideHCID 42602276HCID 42602276, compound

Product 1

HCID 42602277HCID 42602277, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-(1-((3,5-bis(trifluoromethyl)benzyloxy)methyl)-1,3-dihydroisobenzofuran-1-yl)ethanamine (40 mg, 95.4 μmol) in acetonitrile (2 mL) at 0° C. was added formalin (0.250 mL) and then sodium cyanoborohydride (30 mg, 0.48 mmol). The ice bath was removed and stirring continued for 1 h, occasionally treating with a drop of acetic acid to keep the pH slightly less than 7. The reaction was concentrated, diluted with ether, washed with 1 M sodium hydroxide, then brine, dried over sodium sulfate, and concentrated. Column chromatography (4% MeOH/DCM) gave 28.5 mg (67%) as a colorless oil. 1H-NMR (CDCl3, 300 MHz) δ 7.75 (s, 1H), 7.64 (s, 2H), 7.30 (m, 2H), 7.15-7.25 (m, 2H), 5.11 (qAB, JAB=120.5 Hz, 2H), 4.62 (qAB, JAB=13.4 Hz, 2H), 3.67 (qAB, JAB=10.1 Hz, 2H), 2.41 (ddd, J=11.3, 11.3, 5.5 Hz, 1H), 2.20 (s, 6H), 2.19 (m, 1H), 1.98-2.14 (m, 2H); 13C-NMR (CDCl3, 126 MHz) δ 141.3, 141.2, 139.9, 131.7 (q, J=33.6 Hz), 128.2, 127.6, 126.1, 123.4 (q, J=273 Hz), 121.6, 121.4, 121.1, 89.5, 76.8, 72.9, 72.0, 54.3, 45.4, 34.4. Mass spec.: 448.22 (MH)+. Accurate mass spec.: m/z 448.1711 [MH]+, Δ=0.6 ppm.

Workup

  1. customThe ice bath was removed
  2. additionoccasionally treating with a drop of acetic acid
  3. concentrationThe reaction was concentrated
  4. additiondiluted with ether
  5. washwashed with 1 M sodium hydroxide
  6. dry with materialbrine, dried over sodium sulfate
  7. concentrationconcentrated
  8. customColumn chromatography (4% MeOH/DCM) gave 28.5 mg (67%) as a colorless oil

Sources & evidence

ORD record
ord-f1ee80a862054a8a8dc3f611d41e669a
Source dataset
uspto-grants-2009_12
Patent number
US07632861B2

Reaction notes

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