Methanol → HCID 58017385, compound

HRID 451990Notes

Reaction equation

HRID 451990 reaction equation
C1(C)C=CC=CC=1.[Cl:8][C:9]1[CH:10]=[C:11]([CH:27]=[CH:28][C:29]=1[F:30])[C:12]([C@@H:14]1[CH2:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:15]1)=[O:13].CO>C1COCC1.CCOC(C)=O>[Cl:8][C:9]1[CH:10]=[C:11]([C@H:12]([OH:13])[C@@H:14]2[CH2:19][CH2:18][CH2:17][N:16]([C:20]([O:22][C:23]([CH3:25])([CH3:24])[CH3:26])=[O:21])[CH2:15]2)[CH:27]=[CH:28][C:29]=1[F:30]

Participants

6

Reactant 3

HCID 887MethanolHCID 1140TolueneHCID 58017422HCID 58017422, compound

Product 1

HCID 58017385HCID 58017385, compoundYield 32%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1 M R-CBS-oxazaborolidine in toluene (13.8 mL, 13.8 mmol, 0.15 eq) and 10 M BH3 in THF (9.2 mL, 92.4 mmol, 1.0 eq) at −15° C. under nitrogen was added dropwise a solution of (R)-tert-butyl 3-(3-chloro-4-fluorobenzoyl)piperidine-1-carboxylate (31.5 g, 92.4 mmol) in anhydrous THF (300 mL). After addition, the reaction mixture was stirred for 1 hr at rt. Methanol (200 mL) was added dropwise carefully at 0° C. The solvent was removed under reduced pressure to provide the crude product. The crude product was dissolved in EtOAc till the alcohol was just dissolved (about 5 mL/1 g), the solvent was removed on the rotary evaporator until a few crystals appeared. To the above solution was added petroleum ether (about 300 mL) under stirring, which was allowed to stir at rt for 2 hr and then filtered, the crystals were washed with petroleum ether and re-crystallized 6 times to afford the (R)-tert-butyl 3-((R)-(3-chloro-4-fluorophenyl)(hydroxy)methyl)piperidine-1-carboxylate (10 g, 32%, 93% e.e.). 1H NMR (CD3OD, 400 MHZ) δ 7.44 (d, 1H), 7.25 (d, 1H), 7.20 (t, 1H), 4.34 (d, 1H), 4.20 (s, 1H), 3.93 (d, 1H), 2.68 (m, 2H), 1.62 (m, 2H), 1.41 (s, 9H), 1.32 (m, 2H), 1.21 (m, 1H).

Workup

  1. additionAfter addition
  2. customThe solvent was removed under reduced pressure
  3. customto provide the crude product
  4. dissolutionwas just dissolved (about 5 mL/1 g)
  5. customthe solvent was removed on the rotary evaporator until a few crystals
  6. additionTo the above solution was added petroleum ether (about 300 mL)
  7. stirringunder stirring
  8. stirringto stir at rt for 2 hr
  9. filtrationfiltered
  10. washthe crystals were washed with petroleum ether
  11. customre-crystallized 6 times

Sources & evidence

ORD record
ord-db8dc960bc1041e49f22f0f2ed60576e
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

Loading…