Acetic Acid → HCID 22293389, compound

HRID 351475Notes

Reaction equation

HRID 351475 reaction equation
C[O:2][C:3]([C:5]1([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:10]([CH:11]=O)[CH2:9][CH2:8][N:7]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:6]1)=O.C(O)(=O)C.[CH3:31][NH2:32].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C>[CH2:20]([C:5]12[C:3](=[O:2])[N:32]([CH3:31])[CH2:11][CH:10]1[CH2:9][CH2:8][N:7]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:6]2)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6329MethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 57133944HCID 57133944, compound

Product 1

HCID 22293389HCID 22293389, compound

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of the compound of Example 200, Step C (0.210 g, 0.60 mmol) in dichloroethane (5 mL) in a resealable tube was added acetic acid (0.188 mL, 3.28 mmol), methyl amine (2.0 M in MeOH, 1.64 mL, 3.28 mmol) and NaB(OAc)3H (0.951 g, 4.48 mmol), the tube was sealed and the reaction mixture was heated to 70° C. for 30 h. The reaction mixture was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate solution. The organic layer was removed and the aqueous layer was washed twice with CH2Cl2, the combined organic layers were washed with a saturated aqueous brine solution, dried over Na2SO4, filtered and concentrated under vacuum. Purification by silica gel chromatography employing 5-20% EtOAc/CH2Cl2 as the eluant afforded the less polar isomer of Example 200, Step D (0.034 g) as well as the more polar isomer (0.046 g). Example 200, Step D less polar isomer. +APcl MS (M+1)+ 355; 1H NMR (400 MHz, CDCl3) δ: 7.03-7.37 (arom, series of m, 10 H), 3.54 (m, 2H), 3.24 (m, 1H), 2.70 (s, 3H). More polar isomer: +APcl MS (M+1)+ 355; 1H NMR (400 MHz, CDCl3) δ: 7.15-7.33 (arom, series of m, 10 H), 3.59 (d, 1H), 3.43 (d, 1H), 2.74 (s, 3H).

Workup

  1. customthe tube was sealed
  2. customThe reaction mixture was partitioned between CH2Cl2 and saturated aqueous sodium bicarbonate solution
  3. customThe organic layer was removed
  4. washthe aqueous layer was washed twice with CH2Cl2
  5. washthe combined organic layers were washed with a saturated aqueous brine solution
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customPurification by silica gel chromatography
  10. customafforded the less polar isomer of Example 200, Step D (0.034 g) as well as the more polar isomer (0.046 g)

Sources & evidence

ORD record
ord-a0238d5030164e2d987d8869d5d5ce4f
Source dataset
uspto-grants-2004_06
Patent number
USRE038524E1

Reaction notes

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