Pivalaldehyde → HCID 67417662, compound

HRID 913190Notes

Reaction equation

HRID 913190 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@@H:12]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=1)[CH2:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH2:7]2.[CH3:30][C:31]([CH3:35])([CH3:34])[CH:32]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:30][C:31]([CH3:35])([CH3:34])[CH2:32][NH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([C@@H:12]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=1)[CH2:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH2:7]2

Participants

5

Reactant 3

HCID 12417PivalaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 66718493HCID 66718493, compound

Product 1

HCID 67417662HCID 67417662, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of (3R)-3-(7-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethylpropionamide (0.5 g, 1.3 mmol) and trimethylacetaldehyde (0.26 mL, 2.3 mmol) in 1,2-dichloroethane (10 mL), was added sodium triacetoxyborohydride (0.53 g, 2.5 mmol) at room temperature. After 1 day, the mixture was extracted with methylene chloride (50 mL) and water (20 mL). The organic layer was washed with sodium hydrogen carbonate (sat, 25 mL) and brine (25 mL), and dried over MgSO4. Removal of solvent gave a yellow oil, which was purified by prep HPLC to give (3R)-3-[7-(2,2-dimethyl-propylamino)-1-oxo-1,3-dihydro-isoindol-2-yl]-3-(3-ethoxy-4-methoxyphenyl)-N,N-dimethyl-propionamide as a white solid (0.59 g, 99% yield): mp 111-113° C.; 1H NMR (CDCl3) δ 1.01 (s, 9H, 3 CH3), 1.43 (t, J=7 Hz, 3H, CH3), 2.89 (s, 3H, CH3), 2.98 (d, J=6 Hz, 2H, CH2), 3.07 (dd, J=6, 15 Hz, 1H, CHH), 3.11 (s, 3H, CH3), 3.45 (dd, J=9, 15 Hz, 1H, CHH), 3.84 (s, 3H, CH3), 4.08 (q, J=7 Hz, 2H, CH2), 4.12 (d, J=16 Hz, 1H, C), 4.33 (d, J=16 Hz, 1H, CHH), 5.59 (dd, J=7, 9 Hz, 1H, NCH), 6.47-6.51 (m, 2H, Ar), 6.79-7.01 (m, 4H, NH, Ar), 7.22 (t, J=8 Hz, 1H, Ar); 13C NMR (CDCl3) δ 14.75, 27.63, 32, 27, 35.52, 36.67, 37.54, 48.56, 53.10, 54.49, 55.95, 64.42, 107.82, 108.77, 111.25, 112.66, 114.58, 119.22, 132.35, 132.96, 143.09, 148.16, 148.41, 148.81, 169.97, 170.79. Analy. calculated for C27H37N3O4: C, 69.35; H, 7.98; N, 8.99. Found: C, 69.70; H, 7.95; N, 8.74.

Workup

  1. extractionthe mixture was extracted with methylene chloride (50 mL) and water (20 mL)
  2. washThe organic layer was washed with sodium hydrogen carbonate (sat, 25 mL) and brine (25 mL)
  3. dry with materialdried over MgSO4
  4. customRemoval of solvent
  5. customgave a yellow oil, which
  6. customwas purified by prep HPLC

Sources & evidence

ORD record
ord-a6573b2ac33841a18f146a7abad7c0c2
Source dataset
uspto-grants-2011_09
Patent number
US08026269B2

Reaction notes

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