Acetyl chloride → HCID 58508362, compound

HRID 1948810Notes

Reaction equation

HRID 1948810 reaction equation
[CH3:1][C@@H:2]1[NH:7][C@H:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:5][O:4][C:3]1=[O:14].C([O-])([O-])=O.[Na+].[Na+].[C:21](Cl)(=[O:23])[CH3:22]>ClCCl>[C:21]([N:7]1[C@H:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:5][O:4][C:3](=[O:14])[C@@H:2]1[CH3:1])(=[O:23])[CH3:22]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 10340Sodium CarbonateHCID 15042723HCID 15042723, compound

Product 1

HCID 58508362HCID 58508362, compoundYield 74.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a vigorously stirred mixture of (3S,5R)-3-methyl-5-phenyl-3,4,5,6-tetrahydro-2H-1,4-oxazin-2-one (300 mg, 1.56 mmol), Na2CO3 (500 mg, 4.68 mmol, 3.0 equiv.) in anhydrous dichloromethane (30 mL) was added acetyl chloride (0.17 mL, 2.34 mmol, 1.5 equiv.) dropwise over 1 min. The resulting solution was stirred for 15 minutes under an atmosphere of nitrogen. The reaction was quenched by the addition of saturated Na2CO3 (20 mL), the aqueous phase was extracted with diethyl diethyl ether (3×10 mL) and the combined extracts were dried over MgSO4. The solvents were removed in vacuo and the crude material was purified by flash column chromatography on silica, eluting with diethyl ether and dichloromethane (9:1) to furnish the title compound as fine colourless needles (270 mg, 74%); m.p. 82-85° C.; V(max) (KBr) 2943 (C—H), 1733 (C═O, lactone), 1647 (C═O, amide) cm″1; δH (250 MHz, DMSO-d) 7.42-7.36 (5H, m, Ph), 5.49 (0.4H, PhCH×0.4) 5.33 (0.6H, PhCH×0.6), 5.08-5.05 (1H, m, CH3CH), 4.65 (2H, d, J=6.10 Hz, CH2); 2.13 (1H, s, CH3CON×1), 1.86 (2H, s, CH3CON×2), 1.39 (3H, d, J=12.40 Hz CH3CH); δc (62.5 MHz, DMSO-O 170.5, 169.8, 137.8, 129.4, 128.4, 127.1, 68.6, 55.5, 50.7, 49.7, 22.7, 19.0; mIτ (CL, NH3), 234 (MH+, 8%), 233 (M, 13%), 220 (4%), and 219 (100%); HRMS for C13H16NO3 requires 234.1126, found 234.1130; [α]D20−29.8 (c 1.16 CHCl3).

Workup

  1. customThe reaction was quenched by the addition of saturated Na2CO3 (20 mL)
  2. extractionthe aqueous phase was extracted with diethyl diethyl ether (3×10 mL)
  3. dry with materialthe combined extracts were dried over MgSO4
  4. customThe solvents were removed in vacuo
  5. customthe crude material was purified by flash column chromatography on silica
  6. washeluting with diethyl ether and dichloromethane (9:1)

Sources & evidence

ORD record
ord-56b6856e4f084f339c2be2d9e2432128
Source dataset
uspto-grants-2013_03
Patent number
US08399612B2

Reaction notes

Loading…