(2R)-2-[(tert-Butoxycarbonyl)amino]-3-(3'-chloro-4'-fluoro[1,1'-biphenyl]-4-yl)propanoic acid → HCID 68867928, compound

HRID 1984819Notes

Reaction equation

HRID 1984819 reaction equation
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[C:22]([Cl:27])[CH:21]=2)=[CH:16][CH:15]=1)[C:10](O)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2]>C1COCC1>[C:1]([O:5][C:6](=[O:7])[NH:8][C@@H:9]([CH2:10][OH:11])[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[C:22]([Cl:27])[CH:21]=2)=[CH:16][CH:15]=1)([CH3:2])([CH3:4])[CH3:3]

Participants

3

Reactant 1

HCID 57354270(2R)-2-[(tert-Butoxycarbonyl)amino]-3-(3'-chloro-4'-fluoro[1,1'-biphenyl]-4-yl)propanoic acid

Product 1

HCID 68867928HCID 68867928, compoundYield 83.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(2R)-tert-Butoxycarbonylamino-3-(3′-chloro-4′-fluoro-biphenyl-4-yl)-propionic acid (2.0 g, 5.07 mmol) was dissolved in 15 mL anhydrous THF and BH3:THF (11 mL, 11.0 mmol, 1M solution in THF) was added dropwise at 0° C. and stirred for 10 h at room temperature. Excess BH3:THF was quenched by adding methanol (˜1 mL) at 0° C. Solvent was removed under vacuum and residue was dissolved in EtOAc (20 mL) and washed with water, brine and dried over Na2SO4. Solvent was removed under vacuum and silica gel column chromatography (CH2Cl2:MeOH) gave (R)-[2-(3′-chloro-4′-fluoro-biphenyl-4-yl)-1-hydroxymethyl-ethyl]-carbamic acid tert-butyl ester as white solid (1.6 g).

Workup

  1. customExcess BH3:THF was quenched
  2. additionby adding methanol (˜1 mL) at 0° C
  3. customSolvent was removed under vacuum and residue
  4. dissolutionwas dissolved in EtOAc (20 mL)
  5. washwashed with water, brine
  6. dry with materialdried over Na2SO4
  7. customSolvent was removed under vacuum and silica gel column chromatography (CH2Cl2:MeOH)

Sources & evidence

ORD record
ord-0b7183a89dea4224832daa4ac14ba271
Source dataset
uspto-grants-2009_06
Patent number
US07544699B2

Reaction notes

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