Tetrahydrofuran → HCID 58631212, compound

HRID 1487544Notes

Reaction equation

HRID 1487544 reaction equation
C1COCC1.[C:6]([O:10][C:11]([N:13]1[C@H:17]([CH2:18][F:19])[C@@H:16]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[O:30][N:29]=[C:28]([C:31](OCC)=[O:32])[CH:27]=3)=[CH:22][CH:21]=2)[O:15][C:14]1([CH3:37])[CH3:36])=[O:12])([CH3:9])([CH3:8])[CH3:7].[BH4-].[Na+]>CO>[F:19][CH2:18][C@@H:17]1[C@@H:16]([C:20]2[CH:25]=[CH:24][C:23]([C:26]3[O:30][N:29]=[C:28]([CH2:31][OH:32])[CH:27]=3)=[CH:22][CH:21]=2)[O:15][C:14]([CH3:37])([CH3:36])[N:13]1[C:11]([O:10][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:12]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 4311764Sodium borohydrideHCID 58631154HCID 58631154, compound

Product 1

HCID 58631212HCID 58631212, compoundYield 97.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a cooled (0° C.) THF (25 ml) solution of ethyl 5-(4-((4S,5R)-3-(tert-butoxycarbonyl)-4-(fluoromethyl)-2,2-dimethyloxazolidin-5-yl)phenyl)isoxazole-3-carboxylate (1.0 g, 2.2 mmol) is added sodium borohydride (0.25 g, 6.7 mmol) followed by methanol (3 ml added slowly). The reaction is stirred for 30 minutes at 0° C. and for one hour at room temperature. The excess sodium borohydride is quenched by the addition of saturated aqueous ammonium chloride (5 ml). The reaction mixture is diluted with ethyl acetate (50 ml) and water (25 ml). The layers were mixed and allowed to separate. The organic phase is collected, dried over sodium sulfate and concentrated to give the product, (4S,5R)-tert-butyl 4-(fluoromethyl)-5-(4-(3-(hydroxymethyl)isoxazol-5-yl)phenyl)-2,2-dimethyl-oxazolidine-3-carboxylate (875 mg, 96%), as a viscous oil. 1H NMR (400 MHz, CDCl3) 1.52 (s, 9H) 1.59 (s, 3H) 1.74 (br. s., 3H) 2.03-2.08 (m, 1H) 3.83-3.96 (m, 1H) 4.40-4.60 (m, 2H) 4.85 (d, J=6.06 Hz, 2H) 5.19 (d, J=7.58 Hz, 1H) 6.63 (s, 1H) 7.57 (d, J=8.34 Hz, 2H) 7.82 (d, J=8.34 Hz, 2H); m/z (CI) 407 ([M+H]+.

Workup

  1. additionadded slowly)
  2. customThe excess sodium borohydride is quenched by the addition of saturated aqueous ammonium chloride (5 ml)
  3. additionThe reaction mixture is diluted with ethyl acetate (50 ml) and water (25 ml)
  4. additionThe layers were mixed
  5. customto separate
  6. customThe organic phase is collected
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-56abcf0efc7d46e682526cf94f58322e
Source dataset
uspto-grants-2016_08
Patent number
US09428528B2

Reaction notes

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