N-(tert-butoxycarbonyl)glycine → HCID 86587849, compound

HRID 392846Notes

Reaction equation

HRID 392846 reaction equation
[C:1]([NH:9][C@@H:10]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22]C(C)(C)C)=O)[C:11]([O:13][CH3:14])=[O:12])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.O1CCOCC1.[C:34]([O:38][C:39]([NH:41][CH2:42]C(O)=O)=[O:40])([CH3:37])([CH3:36])[CH3:35].C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CCOC(C)=O>[C:1]([NH:9][C@@H:10]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:22])[CH2:42][NH:41][C:39]([O:38][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:40])[C:11]([O:13][CH3:14])=[O:12])(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 2733179PyBroPHCID 204431481,4-Dioxane hydrochlorideHCID 86587850HCID 86587850, compound

Product 1

HCID 86587849HCID 86587849, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A solution of Compound 9 (4.4 g, 12.1 mmol) in CH2Cl (5.0 mL) was treated with 4 N HCl-dioxane (10.0 mL) and stirred for 3 h at 25° C. Solvent and excess acid were removed under reduced pressure, and the residue was dissolved in DMF (150 mL) and treated with N-((tert-butyloxy)carbonyl)glycine (2.2 g, 12.1 mmol), PyBrOP (7.0 g, 15 mmol), and i-Pr2NEt (8.4 mL, 48.4 mmol) and stirred at 25° C. After 12 h the reaction mixture was diluted with EtOAc (500 mL) and washed with 10% aqueous HCl (3×250 mL), 5% aqueous Na2CO3 (250 mL) and saturated aqueous NaCl (250 mL), dried Na2SO4) and evaporated. Flash Chromatography (SiO2, EtOAc) provided 4.6 (90%) of Compound 10 as colorless oil: [α]D25−10.3 (c 0.30, CH3OH); 1H NMR (CDCl3, 400 MHz) δ 7.84 (m, 2H), 7.51 (m, 1H), 7.44 (m, 2H), 6.91 (d, J−7.6 Hz, 1H), 6.35 (brt, J−5.3 Hz, 1H), 5.22 (m, 1H), 4.76 (m, 1H), 3.76 (s, 3H), 3.70 (brt, J−6.3 Hz, 4H), 3.26 (m, 2H), 1.95 (m, 1H), 1.84 (m, 1H), 1.57-1.30 (m, 4H), 1.41 (s, 9H); 13C NMR (CDCl3, 100 MHz) δ 173.0, 169.7, 167.3, 156.5, 133.7, 131.8, 128.6, 127.2, 81.8, 52.5, 52.3, 44.3, 38.7, 32.0, 28.9, 28.3, 22.4; IR (film) νmax 3318, 2954, 1718, 1647, 1535, 1491 cm−1; MALDIFTMS m/z 444.2108 (M+Na+, C21H31N3O6 requires 444.2110).

Workup

  1. customSolvent and excess acid were removed under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (150 mL)
  3. stirringstirred at 25° C
  4. washwashed with 10% aqueous HCl (3×250 mL), 5% aqueous Na2CO3 (250 mL) and saturated aqueous NaCl (250 mL), dried Na2SO4) and
  5. customevaporated

Sources & evidence

ORD record
ord-1c81c7eabc7d4264ae97bef308b8ebc2
Source dataset
uspto-grants-2004_10
Patent number
US06803383B2

Reaction notes

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