Tetrahydrofuran → HCID 58109629, compound

HRID 2037585Notes

Reaction equation

HRID 2037585 reaction equation
[CH2:1]([C@@:4]1([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]2[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][CH2:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])[CH2:12]2)[CH2:6][CH2:5]1)[CH:2]=[CH2:3].C1C[O:37]CC1>>[F:33][C:30]1[CH:29]=[CH:28][C:27]([C@:4]2([CH2:1][CH2:2][CH2:3][OH:37])[O:9][C:8](=[O:10])[N:7]([C@H:11]3[CH2:16][CH2:15][CH2:14][N:13]([C:17]([O:19][CH2:20][C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)=[O:18])[CH2:12]3)[CH2:6][CH2:5]2)=[CH:32][CH:31]=1

Participants

3

Reactant 2

HCID 8028Tetrahydrofuran2×HCID 58109226HCID 58109226, compound

Product 1

HCID 58109629HCID 58109629, compoundYield 20%

Procedure

To a solution of (S)-benzyl 3-((R)-6-allyl-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-3-yl)piperidine-1-carboxylate (78 mg, 0.17 mmol) in THF (3 mL) was added BH3 THF (0.5 mL, 1 mol/L) at 0° C. under nitrogen atmosphere. The formed mixture was stirred for 2 h. The reaction was quenched with water. Then aqueous NaOH solution (3 mol/L, 0.2 mL) and H2O2 (30%, 0.4 mL) was added to the above mixture. The resulting mixture was stirred for 1.5 h. The mixture was extracted with EtOAc, and the combined organic phase was concentrated to give the crude product, which was purified by preparative TLC to give (S)-benzyl 3-((R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-2-oxo-1,3-oxazinan-3-yl)piperidine-1-carboxylate (15 mg, 20%). LC-MS Method 2 tR=1.299 min, m/z=493.1; 1H NMR (CDCl3): 1.12-1.35 (m, 2H), 1.46 (m, 1H), 1.57-1.28 (m, 4H), 1.82-1.98 (m, 2H), 2.11 (m, 1H), 2.23 (m, 1H), 2.46-2.73 (m, 3H), 3.11 (m, 1H), 3.50 (m, 2H), 3.86-4.03 (m, 1H), 5.06 (m, 2H), 6.89-7.01 (m, 2H), 7.16 (m, 2H), 7.23-7.33 (m, 4H).

Workup

  1. customThe reaction was quenched with water
  2. additionThen aqueous NaOH solution (3 mol/L, 0.2 mL) and H2O2 (30%, 0.4 mL) was added to the above mixture
  3. stirringThe resulting mixture was stirred for 1.5 h
  4. extractionThe mixture was extracted with EtOAc
  5. concentrationthe combined organic phase was concentrated
  6. customto give the crude product, which
  7. customwas purified by preparative TLC

Sources & evidence

ORD record
ord-39706ca85ba642dc93cb7bfbc7497702
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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