Formaldehyde → HCID 86753770, compound

HRID 1417542Notes

Reaction equation

HRID 1417542 reaction equation
N[C@H:2]1[CH2:22][CH2:21][C@:4]2([O:8][CH2:7][C:6]([C:9]3[CH:14]=[C:13]([C:15]#[N:16])[CH:12]=[CH:11][C:10]=3[O:17][CH:18]([CH3:20])[CH3:19])=[CH:5]2)[C@H:3]1[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1.O.[CH2:31]=O.[C:33]([BH3-])#[N:34].[Na+]>C(#N)C.C(O)(=O)C.C(#N)C>[CH3:31][N:34]([CH3:33])[C@H:2]1[CH2:22][CH2:21][C@:4]2([O:8][CH2:7][C:6]([C:9]3[CH:14]=[C:13]([C:15]#[N:16])[CH:12]=[CH:11][C:10]=3[O:17][CH:18]([CH3:20])[CH3:19])=[CH:5]2)[C@H:3]1[C:23]1[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 712FormaldehydeHCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 56974608HCID 56974608, compound

Product 1

HCID 86753770HCID 86753770, compound

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 22391770Acetonitrile aceticacidSolvent

Procedure

(5R,6S,7S)-7-Amino-6-(4-fluorophenyl)-3-(5-cyano-2-isopropoxy-phenyl)-1-oxaspiro[4.4]non-3-ene (17.7 mg, 0.045 mmol) was taken up in acetonitrile (0.72 mL). Water (0.2 mL) and 37% formaldehyde (33 μL) were added followed by a solution of sodium cyanoborohydride (11.2 mg, 0.178 mmol) in acetonitrile (0.2 mL). The reaction mixture was stirred for 1 hour at room temperature with occasional addition of 20% acetic acid/acetonitrile to maintain the pH of the reaction at ~7. The mixture was evaporated, and the residue was partitioned between ethyl acetate and 2.5N NaOH. The organic layer was washed with saturated brine solution and evaporated. Pure title compound (12.3 mg) was obtained by silica gel chromatography eluting with 5-10% methanol/methylene chloride. 400 MHz 1H NMR (CD3OD): δ 1.28 (d, 3H), 1.31 (d, 3H), 2.28 (s, 6H), 3.17 (d, 1H), 3.68 (m, 1H), 4.10 (dd, 1H), 4.65-4.75 (m, 2H), 6.32 (m, 1H), 6.96 (t, 2H), 7.08 (d, 1H), 7.38 (m, 3H), 7.53 (dd, 1H).

Workup

  1. temperatureto maintain
  2. customthe pH of the reaction at ~7
  3. customThe mixture was evaporated
  4. customthe residue was partitioned between ethyl acetate and 2.5N NaOH
  5. washThe organic layer was washed with saturated brine solution
  6. customevaporated

Sources & evidence

ORD record
ord-3779f1bf2fa04397a051abc5d3ddfb0c
Source dataset
uspto-grants-1999_03
Patent number
US05877191

Reaction notes

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