Methanol → tert-butyl (2S,3R)-3-hydroxy-1-phenylpent-4-en-2-ylcarbamate

HRID 654305Notes

Reaction equation

HRID 654305 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:10](=[O:13])[CH:11]=[CH2:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].CO.O.O.O.O.O.O.O.[Cl-].[Ce+3].[Cl-].[Cl-].[BH4-].[Na+]>ClCCl.C(O)C.C(OCC)(=O)C.CCCCCC>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[C@H:10]([OH:13])[CH:11]=[CH2:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 4

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 15296047tert-butyl (1S)-1-benzyl-2-oxobut-3-enylcarbamateHCID 21585214Cerium trichloride heptahydrate

Product 1

HCID 11065740tert-butyl (2S,3R)-3-hydroxy-1-phenylpent-4-en-2-ylcarbamateYield 51.8%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6344DichloromethaneSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 3.03 g (11 mmol) of the resultant compound of Example 1 in 120 ml of 1:1 dichloromethane:methanol was cooled to 0° C., and treated with 4.10 g (11 mmol) of cerium(III) chloride heptahydrate. The resulting solution was immediately cooled to -78° and treated slowly with a solution of 0.63 g (16.5 mmol) of sodium borohydride in 15 ml of ethanol in such a way that the ethanolic solution was precooled by the side of the flask. After 1 h, the solution was quenched by addition of aqueous ammonium chloride, extracted with ether, washed sequentially with aqueous NaHCO3 and saturated brine, dried over MgSO4 and concentrated in vacuo to give a 4.7:1 ratio of diastereomeric products. Silica gel chromatography of the residue using 3:1 hexane:ethyl acetate provided 1.58 g (52%) of the pure desired compound (Rf 0.35, 15% ethyl acetate in chloroform) as a white solid (m.p. 122°-124° C.), along with 0.22 g (7%) of (3R,4S)-4-(t-butyloxycarbonylamino)-3-hydroxy-5-phenyl-1-pentene. 1H NMR (CDCl3) δ 1.37 (s, 9 H), 2.73 (dd, J=15, 9 Hz 1 H), 2.85 (dd J=15, 5 Hz, 1 H), 2.98 (m, 1 H), 3.98 (m, 1 H), 4.24 (m, 1 H), 4.58 (br, 1 H), 5.29 (dt, J=10, 1.5 Hz, 1 H), 5.38 (dt, J=17, 1.5 Hz, 1 H), 5.94 (ddd, J=17, 10, 6 Hz, 1 H), 7.2-7.3 (m, 5 H).

Workup

  1. temperatureThe resulting solution was immediately cooled to -78°
  2. customthe solution was quenched by addition of aqueous ammonium chloride
  3. extractionextracted with ether
  4. washwashed sequentially with aqueous NaHCO3 and saturated brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto give a 4.7:1 ratio of diastereomeric products

Sources & evidence

ORD record
ord-8e179f64f15f48719d3e3d7a234a5628
Source dataset
uspto-grants-1992_07
Patent number
US05130468

Reaction notes

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