1,1-Dimethylethyl (2S,3R)-6-oxo-2,3-diphenyl-4-morpholinecarboxylate → tert-Butyl (3R,5R,6S)-2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate

HRID 1778585Notes

Reaction equation

HRID 1778585 reaction equation
[O:1]=[C:2]1[CH2:7][N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:5]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C@H:4]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[O:3]1.I[CH2:28][CH2:29][CH2:30][CH2:31][B:32]1[O:36][C:35]([CH3:38])([CH3:37])[C:34]([CH3:40])([CH3:39])[O:33]1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1.CN(P(N(C)C)(N(C)C)=O)C>[O:1]=[C:2]1[O:3][C@@H:4]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C@@H:5]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:6]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@@H:7]1[CH2:28][CH2:29][CH2:30][CH2:31][B:32]1[O:36][C:35]([CH3:38])([CH3:37])[C:34]([CH3:39])([CH3:40])[O:33]1

Participants

6

Reactant 3

HCID 9812251,1-Dimethylethyl (2S,3R)-6-oxo-2,3-diphenyl-4-morpholinecarboxylateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 66833241HCID 66833241, compound

Product 1

HCID 66833293tert-Butyl (3R,5R,6S)-2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylateYield 94%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

A solution of (2S,3R)-tert-butyl 6-oxo-2,3-diphenylmorpholine-4-carboxylate (4.69 g, 13.27 mmol) and 2-(4-iodobutyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (d 1.38, 5.96 mL, 8.23 g, 26.5 mmol, 2 equiv) in THF (66 mL, 0.2 M) and HMPA (6.6 mL) was cooled to −78° C. and treated with sodium bis(trimethylsilyl)amide (14.6 mL, 1.0 M, 1.1 equiv) drop wise over 5 min and stirred for 1 h. After warming to room temperature and stirring for an additional 2 h, the solution was cooled to 0° C. and quenched with 0.5 N HC (2-3 equiv). The resulting solution was diluted with heptane and washed successively with water and saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. Purification by MPLC (1-60% ethyl acetate in heptane over 6 CV) gave (3R,5R,6S)-tert-butyl 2-oxo-5,6-diphenyl-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl)morpholine-4-carboxylate as a white solid (6.66 g, 94%); ESI-LCMS m/z calcd for C31H42BNO2: expected 535.3. found 536.4 (M+H)+.

Workup

  1. stirringstirring for an additional 2 h
  2. temperaturethe solution was cooled to 0° C.
  3. customquenched with 0.5 N HC (2-3 equiv)
  4. additionThe resulting solution was diluted with heptane
  5. washwashed successively with water and saturated aqueous NaCl
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customPurification by MPLC (1-60% ethyl acetate in heptane over 6 CV)

Sources & evidence

ORD record
ord-fc1d6253ea1b485bbbbef5f16156be75
Source dataset
uspto-grants-2016_02
Patent number
US09266908B2

Reaction notes

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