Tetrahydrofuran → HCID 53473230, compound

HRID 2037526Notes

Reaction equation

HRID 2037526 reaction equation
[CH2:1]([C@@:4]1([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[F:32])[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].C1C[O:36]CC1>>[F:25][C:22]1[CH:23]=[CH:24][C:19]([C:16]2[CH:17]=[CH:18][C:13]([C@@H:11]([N:7]3[CH2:6][CH2:5][C@@:4]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=4[F:32])([CH2:1][CH2:2][CH2:3][OH:36])[O:9][C:8]3=[O:10])[CH3:12])=[CH:14][CH:15]=2)=[CH:20][CH:21]=1

Participants

3

Reactant 2

HCID 8028Tetrahydrofuran2×HCID 58109453HCID 58109453, compound

Product 1

HCID 53473230HCID 53473230, compoundYield 17%

Procedure

To a solution of (R)-6-allyl-3-((S)-1-(4′-fluorobiphenyl-4-yl)ethyl)-6-(2-fluorophenyl)-1,3-oxazinan-2-one (80 mg, 0.18 mmol) in THF (10 mL) was added BH3 THF (1.5 mL, 1 mol/L) at 0° C. under nitrogen. The formed mixture was stirred for 2 h. The reaction was quenched by water. Then aq NaOH (0.3 mL, 3 mol/L) solution and H2O2 (3 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 HPLC to give (R)-3-((S)-1-(4′-fluorobiphenyl-4-yl)ethyl)-6-(2-fluorophenyl)-6-(3-hydroxypropyl)-1,3-oxazinan-2-one (15 mg, 17%). LC-MS Method 2 tR=1.48, min, m/z=452.2; 1H NMR (CD3OD) 1.22-1.34 (m, 2H), 1.53 (d, 3H), 1.62-1.73 (m, 1H), 1.98-2.33 (m, 4H), 2.61 (d, 1H), 3.13 (m, 1H), 3.51 (m, 2H), 5.61 (m, 1H), 7.01-7.19 (m, 5H), 7.23 (m, 1H), 7.31-7.43 (m, 4H), 7.53 (m, 2H).

Workup

  1. customThe reaction was quenched by water
  2. additionThen aq NaOH (0.3 mL, 3 mol/L) solution and H2O2 (3 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 HPLC

Sources & evidence

ORD record
ord-a918127a050f4bcdae36ba8b403751d8
Source dataset
uspto-grants-2013_11
Patent number
US08575156B2

Reaction notes

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