L-Alanine 1,1-dimethylethyl ester → HCID 59843757, compound

HRID 1948817Notes

Reaction equation

HRID 1948817 reaction equation
[C:1]([N:4]1[C@H:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][O:7][C:6](=[O:16])[C@@H:5]1[CH3:17])(=[O:3])[CH3:2].[C:18]([O:22][C:23](=[O:27])[C@H:24]([CH3:26])[NH2:25])([CH3:21])([CH3:20])[CH3:19]>ClCCl>[C:18]([O:22][C:23](=[O:27])[C@H:24]([CH3:26])[NH:25][C:6](=[O:16])[C@H:5]([CH3:17])[N:4]([C:1](=[O:3])[CH3:2])[CH:9]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH2:8][OH:7])([CH3:21])([CH3:20])[CH3:19]

Participants

4

Reactant 2

HCID 89016L-Alanine 1,1-dimethylethyl esterHCID 58508362HCID 58508362, compound

Product 1

HCID 59843757HCID 59843757, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

(3S,5R)-4-N-acetyl-3-methyl-5-phenyl-3,4,5,6,-tetrahydro-2H-1,4-oxazin-2-one (68) (220 mg, 0.94 mmol) and L-alanine tert-butyl ester (66) (205 mg, 1.42 mmol, 1.5 equiv.) were dissolved in anhydrous dichloromethane (14 mL) in a doubly sealed PTFE cylinder and subjected to ultra-high pressure of 19 kbar for 48 hours. After releasing the pressure, the solution was filtered through a short pad of CELITE® diatomaceous earth and removal of solvent from the filtrate in vacuo yielded the crude product which was purified by flash column chromatography on silica eluting with diethyl ether and dichloromethane (4:1) to furnish the title product as fine colourless needles (120 mg, 34%); m.p. 38-40° C.; v(max)(KBr) 3411 (O—H), 2980 (C—H), 1735 (C═O, lactone), 1646 (C═O, amide) cm−1; δH (250 MHz, DMSO-d) 8.06 (0.5H, d, /6.95 Hz, NH×0.5), 7.55-7.24 (5H, m, Ph), 6.54 (0.5H, d, J 6.38 Hz, NH×0.5), 5.82 (0.5H, t, /4.88 Hz, OH×0.5), 5.14-5.06 (1H, m, PhCH), 4.83 (0.5H, t, J 6.56 Hz, OH×0.5), 4.35 (0.5H, q, J 6.99 Hz, CH3CH×0.5), 4.08-4.03 (2H, m, CH2OH), 3.98-3.76 (1.5H, m, CHCH3×0.5 and CHCH3×1), 2.23 (1.5H, s, COCH3), 2.14 (1.5H, s, COCH3), 1.46-1.39 (12H, m, CHCH3×3 and C(CH3)3×9), 1.19 (1.5H, d, /7.15 Hz, CHCH3×1.5), 0.97 (1.5H, d, J 7.23 Hz, CHCH3×1.5); δc (62.5 MHz, DMSO-d) 171.8, 171.7, 171.0, 170.8, 170.2, 140.0, 138.2, 129.1, 128.2, 128.0, 126.8, 80.7, 62.7, 62.5, 60.8, 56.3, 53.4, 48.8, 48.7, 27.9, 17.5, 16.9, 16.7, 15.2; m/z (CL, NH3), 379 (MH+, 70%), 361 (18%), 305 (20%), 249 (38%), 234 (100%), and 219 (40%); HRMS for C20H31N2O5 requires 379.2225 found 379.2240; [α]D20 −37.0 (c 1.06 CHCl3).

Workup

  1. filtrationthe solution was filtered through a short pad of CELITE® diatomaceous earth and removal of solvent from the filtrate in vacuo
  2. customyielded the crude product which
  3. customwas purified by flash column chromatography on silica eluting with diethyl ether and dichloromethane (4:1)

Sources & evidence

ORD record
ord-765358b0c1744ff6bf313356a1a55739
Source dataset
uspto-grants-2013_03
Patent number
US08399612B2

Reaction notes

Loading…