Sodium Sulfate → (S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionic acid benzyl ester

HRID 61289

Reaction equation

HRID 61289 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]([CH2:20][OH:21])[C:10]([O:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].S([O-])([O-])(=O)=O.[Na+].[Na+].[F:29][C:30]([F:38])(S(F)(=O)=O)C(O)=O>C(#N)C.C(OCC)C.[Cu]I>[CH2:13]([O:12][C:10](=[O:11])[C@@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:7])[CH2:20][O:21][CH:30]([F:38])[F:29])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

7

Reactant 3

HCID 24436Sodium SulfateHCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acidHCID 12953535N-Boc-DL-serine Benzyl Ester

Product 1

HCID 90041473(S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionic acid benzyl esterYield 40%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 3283Diethyl EtherSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
60 °C

Procedure

To a stirred solution of the compound of Formula XII(a), benzyl 2-(tert-butoxycarbonylamino)-3-hydroxypropanoate (1 g, 3.38 mmol) in acetonitrile (10 mL) was added copper(I) iodide (64.4 mg, 0.338 mmol) and sodium sulfate (48.1 mg, 0.338 mmol). The resulting mixture was stirred at 60° C. and treated with 2,2-difluoro-2-fluorosulfonylacetic acid (524 μL, 5.08 mmol), dropwise, as a solution in acetonitrile (2 mL) over a period of 1.5 h. Upon completion of the addition, the mixture was stirred for a further 30 min then cooled to room temperature. The mixture was diluted with diethyl ether and washed with brine (2×), water (3×) and brine (1×). The organic phase was dried, filtered and concentrated in vacuo then chromatographed in 0-30% ethyl acetate in hexanes, to provide the compound of Formula XIII(a), (S)-2-tert-butoxycarbonylamino-3-difluoromethoxy-propionic acid benzyl ester (458 mg, 40%) as a colorless sticky oil. 1H NMR (300 MHz, CDCl3): δ (ppm) 7.32-7.38 (m, 5H), 6.18 (wt, 1H), 5.28 (dd, 1H), 5.19 (dd, 2H), 4.55 (dt, 1H) 4.22 (td, 1H), 4.15 (m, 2H), 1.38 (s, 9H).

Workup

  1. additionUpon completion of the addition
  2. stirringthe mixture was stirred for a further 30 min
  3. temperaturethen cooled to room temperature
  4. washwashed with brine (2×), water (3×) and brine (1×)
  5. customThe organic phase was dried
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customthen chromatographed in 0-30% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-fdbbf23e8ab34ac6a6515ce0bc08c2cd
Source dataset
uspto-grants-2016_09
Patent number
US09441012B2

Linked notes

Loading…