2-((Tert-butyldimethylsilyl)oxy)acetaldehyde → HCID 11754519, compound

HRID 1768471Notes

Reaction equation

HRID 1768471 reaction equation
[Si]([O:8][CH2:9][C:10]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:14]=[C:13]([C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[F:22])[CH2:12][N:11]1[C:23]([N:25]([CH3:32])[CH:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)=[O:24])(C(C)(C)C)(C)C.[Si]([O:46][CH2:47][CH:48]=O)(C(C)(C)C)(C)C.[BH3-]C#N.[Na+]>CO.CC(O)=O>[F:22][C:16]1[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:15]=1[C:13]1[CH2:12][N:11]([C:23]([N:25]([CH:26]2[CH2:27][CH2:28][N:29]([CH2:48][CH2:47][OH:46])[CH2:30][CH2:31]2)[CH3:32])=[O:24])[C:10]([CH2:9][OH:8])([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:14]=1

Participants

6

Reactant 3

HCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 5003444Sodium cyanoborohydrideHCID 10098834HCID 10098834, compound

Product 1

HCID 11754519HCID 11754519, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 887MethanolSolvent

Procedure

To 150 mg (0.28 mmol) of amine 7-2 in MeOH was added 145 mg (0.83 mmol) of (t-butyldimethylsilyloxy) acetaldehyde and several drops of HOAc. After stirring for 1 h, 35 mg (0.55 mmol) of NaCNBH3 was added and the reaction was stirred overnight in a sealed flask. The mixture was partitioned between EtOAc and saturated NaHCO3, the layers were separated, the organic phase was washed with water, dried over MgSO4, and concentrated by rotary evaporation. The residue was dissolved in dry EtOAc, saturated with HCl(g) and stirred for 1 h. The reaction was partitioned between EtOAc and saturated NaHCO3, the layers were separated, the organic phase was washed with water, dried over MgSO4, and concentrated by rotary evaporation. The residue was purified by reverse phase HPLC, but was not of sufficient purity, so it was then purified by column chromatography on silica gel with 20:1:1 EtOH/NH4OH/H2O in EtOAc to provide 11-1 as a white solid. Data 11-1: 1HNMR (500 MHz, CDCl3) δ 7.4-7.2 (m, 5H), 7.1-6.9 (m, 3H), 6.3 (s, 1H), 5.4 (m, 1H), 4.8 (m, 1H), 4.6 (m, 1H), 4.4 (m, 1H), 4.0 (m, 1H), 3.75 (m, 1H), 3.6 (m, 2H), 3.0 (m, 2H), 2.9 (s, 3H), 2.5 (m, 2H), 2.2 (m, 2H), 1.8 (m, 3H), 1.7 (m, 1H) ppm. HRMS (ES) calc'd M+H for C26H31F2N3O3: 472.2406. Found: 472.2386.

Workup

  1. stirringthe reaction was stirred overnight in a sealed flask
  2. customThe mixture was partitioned between EtOAc and saturated NaHCO3
  3. customthe layers were separated
  4. washthe organic phase was washed with water
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated by rotary evaporation
  7. dissolutionThe residue was dissolved in dry EtOAc, saturated with HCl(g)
  8. stirringstirred for 1 h
  9. customThe reaction was partitioned between EtOAc and saturated NaHCO3
  10. customthe layers were separated
  11. washthe organic phase was washed with water
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated by rotary evaporation
  14. customThe residue was purified by reverse phase HPLC
  15. customwas then purified by column chromatography on silica gel with 20:1:1 EtOH/NH4OH/H2O in EtOAc

Sources & evidence

ORD record
ord-3d540343199a423584698ef647f223f0
Source dataset
uspto-grants-2007_06
Patent number
US07235580B2

Reaction notes

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