Acetic Acid → HCID 59837438, compound

HRID 273030Notes

Reaction equation

HRID 273030 reaction equation
[CH3:1][NH:2][CH2:3][C:4]1([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][CH2:19][N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)=[CH:12][CH:11]=2)[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1.C(O[C:28]1(O[Si](C)(C)C)[CH2:30][CH2:29]1)C.CC(O)=O.[BH3-]C#N.[Na+]>CO>[CH3:1][N:2]([CH2:3][C:4]1([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH2:17][CH2:18][CH2:19][N:20]3[CH2:24][CH2:23][CH2:22][CH2:21]3)=[CH:12][CH:11]=2)[CH2:9][CH2:8][O:7][CH2:6][CH2:5]1)[CH:28]1[CH2:30][CH2:29]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 2734686(1-Ethoxycyclopropoxy)trimethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 11674363Methyl-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]tetrahydropyran-4-ylmethyl}amine

Product 1

HCID 59837438HCID 59837438, compoundYield 15.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of methyl-{4-[4-(3-pyrrolidin-1-ylpropoxy)phenyl]-tetrahydropyran-4-ylmethyl}amine (115 mg, 0.35 mmol), (1-Ethoxy-cyclopropoxy)-trimethylsilane (360 mg, 2.0 mmol), AcOH (0.2 ml, 3.5 mmol), NaCNBH3 (110 mg, 1.75 mmol) and 4 Å molecular sieves (100 mg) in MeOH (5 ml) was heated to reflux for 18 hours. The mixture was cooled, concentrated in vacuo and partitioned between 2M NaOH (10 ml) and DCM (10 ml). The organic phase was separated and the aqueous phase extracted with DCM (2×10 ml). The combined organic phases were concentrated in vacuo and purified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (92:8:1) to provide the title compound as a clear colourless oil (20 mg, 0.054 mmol, 15%). 1H NMR (400 MHz, CDCl3) δ 0.15 (m, 2H), 0.29 (m, 2H), 1.68 (m, 1H), 1.70-1.90 (m, 6H), 1.85 (s, 3H), 2.00-2.10 (m, 4H), 2.60 (m, 4H), 2.65 (s, 2H), 2.68 (m, 2H), 3.50 (t, 2H), 3.76 (m, 2H), 4.01 (t, 2H), 6.85 (d, 2H), 7.16 (d, 2H). HRMS ESI+ m/z 373.2844 [MH]+.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 18 hours
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated in vacuo
  5. custompartitioned between 2M NaOH (10 ml) and DCM (10 ml)
  6. customThe organic phase was separated
  7. extractionthe aqueous phase extracted with DCM (2×10 ml)
  8. concentrationThe combined organic phases were concentrated in vacuo
  9. custompurified by flash chromatography on silica gel eluting with dichloromethane:methanol:ammonia (92:8:1)

Sources & evidence

ORD record
ord-7be40f2b0e504cd397f83e8433507e9a
Source dataset
uspto-grants-2008_11
Patent number
US07456164B2

Reaction notes

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