Diisopropylethylamine → (S)-tert-Butyl 1-(2-(1,3-dioxolan-2-yl)-4-methoxyphenylamino)-3-hydroxy-2-methyl-1-oxopropan-2-ylcarbamate

HRID 709882Notes

Reaction equation

HRID 709882 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@:9]([CH3:15])([CH2:13][OH:14])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.[O:25]1[CH2:29][CH2:28][O:27][CH:26]1[C:30]1[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:31]=1[NH2:32].F[P-](F)(F)(F)(F)F.C[N+](C)=C(N(C)C)ON1C2N=CC=CC=2N=N1>CN(C=O)C.O.C(OCC)(=O)C>[O:25]1[CH2:29][CH2:28][O:27][CH:26]1[C:30]1[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[CH:33][C:31]=1[NH:32][C:10](=[O:12])[C@:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])([CH3:15])[CH2:13][OH:14]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12991620(S)-2-((tert-Butoxycarbonyl)amino)-3-hydroxy-2-methylpropanoic acidHCID 153389082-(1,3-Dioxolan-2-yl)-4-methoxyaniline

Product 1

HCID 70880773(S)-tert-Butyl 1-(2-(1,3-dioxolan-2-yl)-4-methoxyphenylamino)-3-hydroxy-2-methyl-1-oxopropan-2-ylcarbamateYield 43.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

(S)-2-tert-Butoxycarbonylamino-3-hydroxy-2-methyl-propionic acid (247.1 mg, 0.001127 mol) was dissolved in DMF, followed by N,N-diisopropylethylamine (0.892 mL, 0.00512 mol), and then 2-(1,3-dioxolan-2-yl)-4-methoxyaniline (200.0 mg, 0.001024 mol) and N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (389.5 mg, 0.001024 mol) at 23° C. The reaction mixture was allowed to stir at 23° C. for 10 hours. Ethyl acetate (50 mL) was added, followed by water (10 mL). Organic layer was separated, and the aqueous layer was extracted with additional ethyl acetate (2×10 mL). Combined organic layers were washed with water (3×10 mL), brine and dried over Na2SO4. The crude product was purified via chromatography (SiO2, 12 g, 0-50% ethyl acetate/hexanes) to give the desired product (176 mg, 43%). 1H NMR (MeOD) δ: 7.98 (s, 1H), 7.01 (d, J=3.0 Hz, 1H), 6.93 (dd, J=8.9, 2.9 Hz, 1H), 5.76 (s, 1H), 4.13-4.26 (m, 2H), 3.95-4.09 (m, 2H), 3.69-3.85 (m, 7H), 1.37-1.53 (m, 12H). MS (M+1): 397.20.

Workup

  1. customat 23° C
  2. customOrganic layer was separated
  3. extractionthe aqueous layer was extracted with additional ethyl acetate (2×10 mL)
  4. washCombined organic layers were washed with water (3×10 mL), brine
  5. dry with materialdried over Na2SO4
  6. customThe crude product was purified via chromatography (SiO2, 12 g, 0-50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9c41fa5d5b61419aa1b7715af8b1c619
Source dataset
uspto-grants-2015_11
Patent number
US09181191B2

Reaction notes

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