Chloroacetic Acid → HCID 477545, compound

HRID 1456609Notes

Reaction equation

HRID 1456609 reaction equation
[OH:1][C@H:2]1[C:11]2[C:6](=[CH:7][C:8]([O:20][CH:21]([CH3:23])[CH3:22])=[C:9]3[C:15]([CH2:16][CH2:17][CH3:18])=[CH:14][C:13](=[O:19])[O:12][C:10]3=2)[O:5][C@H:4]([CH3:24])[C@H:3]1[CH3:25].N(C(OCC)=O)=NC(OCC)=O.P(C)(C)C.C(Cl)C(O)=O.[OH-].[NH4+]>C1COCC1.C1(C)C=CC=CC=1.CC#N>[OH:1][C@@H:2]1[C:11]2[C:6](=[CH:7][C:8]([O:20][CH:21]([CH3:23])[CH3:22])=[C:9]3[C:15]([CH2:16][CH2:17][CH3:18])=[CH:14][C:13](=[O:19])[O:12][C:10]3=2)[O:5][C@H:4]([CH3:24])[C@H:3]1[CH3:25]

Participants

9

Reactant 5

HCID 300Chloroacetic AcidHCID 14923Ammonium Hydroxide2×HCID 68983TrimethylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 386098HCID 386098, compound

Product 1

HCID 477545HCID 477545, compoundYield 83.5%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6342AcetonitrileSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution 7a (100 mg, 0.28 mmol) in THF (8 mL) and toluene (8 mL), maintained at -78° C., was added diethyl azodicarboxylate (DEAD, 0.455 mL, 2.88 mmol), PMe3 (2.89 mL, 1.0M solution in THF), and chloroacetic acid24 (220 mg, 2.32 mmol). The reaction mixture was stirred at -78° C. and allowed to warm to -30° C. over a period of 1.5 h (until complete disappearance of starting material was observed by TLC). Ammonium hydroxide (5 mL) was then added, and the solution was concentrated under reduced pressure. The residue obtained was then treated with ammonium hydroxide (5 mL) in CH3CN (10 mL), and the mixture was stirred for 4 h. The mixture was then quickly extracted with ether, the organic layer was dried (MgSO4), concentrated, and submitted for silica gel chromatography (Solvent A) to give 81 mg (81%) of 8a as a colorless syrup: [α]D20 +106° (c 1.1, CHCl3); 1H NMR (CDCl3): δ0.99 (t, 3 H, J=7.3 Hz, --CH2CH2CH3), 1.12 (d, 3 H, J=6.8 Hz, --CHCH3), 1.38 and 1.40 [2d, 6 H, J=5.8 Hz, --CH(CH3)2 ], 1.42 [d, 3 H, J=6.5 Hz, --CH(CH3)], 1.60 (m, 2 H, J=7.48 Hz, --CH2CH2 CH3), 1.93 (m, 1 H, H-9), 2.87 (m, 2 H, --CH2CH2 CH3), 3.59 (bs, 1 H, --OH), 3.91 (m, 1 H, H-8), 4.62 [m, 1 H, J=6.0 Hz, --CH(CH3)2 ], 4.70 (d, 1 H, J=7.6 Hz, H-10), 5.92 (s, 1 H, H-3), 6.21 (s, 1 H, H-6); 13C NMR (CDCl3): δ 13.87, 15.73, 18.95, 21.66, 21.80, 23.19, 39.02, 40.48, 66.66, 70.77, 77.00, 96.92, 104.83, 106.14, 110.02, 155.69, 156.15, 157.75, 159.06, 160.48. Anal. Calcd for C20H26O5.0.03CH2Cl2 : C, 65.50; H, 7.21. Found: C, 65.74; H, 7.39.

Workup

  1. temperatureto warm to -30° C. over a period of 1.5 h (until complete disappearance of starting material was observed by TLC)
  2. concentrationthe solution was concentrated under reduced pressure
  3. customThe residue obtained
  4. stirringthe mixture was stirred for 4 h
  5. extractionThe mixture was then quickly extracted with ether
  6. dry with materialthe organic layer was dried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-d8f6ce0a86154eea9badb727aaa0e8e0
Source dataset
uspto-grants-1998_12
Patent number
US05843990

Reaction notes

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