Dichloromethane → (RS)-5-(4-Benzyloxy-phenyl)-4-tertbutoxycarbonylamino-pent-2-enoic acid methyl ester

HRID 852878

Reaction equation

HRID 852878 reaction equation
C(OP([CH2:9][C:10]([O:12][CH3:13])=[O:11])(OCC)=O)C.[C:14]([O:18][C:19](=[O:39])[NH:20][CH:21]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:27][CH:26]=1)[CH:22]=O)([CH3:17])([CH3:16])[CH3:15].[OH-].[Na+].[CH2:42](Cl)Cl>[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:13]([O:12][C:10](=[O:11])[CH:9]=[CH:22][CH:21]([NH:20][C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:39])[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:27][CH:26]=1)[CH3:42].[CH3:13][O:12][C:10](=[O:11])[CH:9]=[CH:22][CH:21]([NH:20][C:19]([O:18][C:14]([CH3:15])([CH3:17])[CH3:16])=[O:39])[CH2:24][C:25]1[CH:26]=[CH:27][C:28]([O:31][CH2:32][C:33]2[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=2)=[CH:29][CH:30]=1

Participants

7

Reactant 4

HCID 6344Dichloromethane2×HCID 14798Sodium HydroxideHCID 66113Methyl diethylphosphonoacetateHCID 10904373tert-butyl N-[1-oxo-3-(4-phenylmethoxyphenyl)propan-2-yl]carbamate

Product 2

HCID 69415650(RS)-5-(4-Benzyloxy-phenyl)-4-tertbutoxycarbonylamino-pent-2-enoic acid methyl esterHCID 69416006(RS)-5-(4-Benzyloxy-phenyl)-4-tertbutoxycarbonylamino-pent-2-enoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 67553Tetrabutylammonium IodideCatalyst

Procedure

A solution of triethyl phosphonoacetate or methyl diethylphosphonoacetate (5.19 mmol) and (RS)-[1-(4-Benzyloxy-benzyl)-2-oxo-ethyl]-carbamic acid tert-butyl ester (1.843 g, 5.19 mmol) in DCM (5 mL) was added dropwise to a vigorously stirred mixture of 50% aq. NaOH (30 mL) and 50 mL DCM containing tetrabutylammonium iodide (1.0 g). After 3 hr, the layers were separated and the organic phase was washed with water (20 mL) and brine (10 mL) then dried (Na2SO4) and evaporated. The crude material was chromatographed (silica gel, 1:4 EtOAc/petroleum) to give either (RS)-5-(4-Benzyloxy-phenyl)-4-tertbutoxycarbonylamino-pent-2-enoic acid ethyl ester 77 or (RS)-5-(4-Benzyloxy-phenyl)-4-tertbutoxycarbonylamino-pent-2-enoic acid methyl ester RS-40 (˜85% yield in each case). Compound 77: 1H nmr (CDCl3) δ 1.28 (t, J=7.1 Hz, 3H), 1.40 (s, 9H), 2.84 (br d, J=6.2 Hz, 2H), 4.19 (q, J=7.1 Hz, 2H), 4.52 (br s, 2H), 5.05 (s, 2H), 5.86 (dd, J=1.5, 15.7 Hz, 1H), 6.91 (dd, J=4.8, 15.6 Hz, 1H), 6.92 (d, J=8.6 Hz, 2H), 7.09 (d J=8.7 Hz, 2H), 7.32-7.45 (m, 5H). 13C nmr (CDCl3) δ 66.1, 157.7, 154.9, 147.7, 137.0, 130.4, 128.6, 127.9, 127.4, 121.0, 115.1, 114.9, 79.8, 70.0, 60.4, 52.4, 40.0, 28.3, 14.2. Compound RS-40: 1H NMR (CDCl3) δ 1.40 (s, 9H), 2.80 (m, 2H), 3.70 (s, 3H), 4.52 (br s, 2H), 5.05 (s, 2H), 5.83 (d, J=15 Hz, 1H), 6.88 (d, J=8.7 Hz, 2H), 6.88 (d, J=15 Hz, 1H), 7.07 (d, J=8.7 Hz, 2H), 7.28-7.48 (m, 5H). 13C NMR (CDCl3) δ 28.5, 40.1, 51.8, 52.6, 70.2, 80.0, 115.1, 120.8, 127.6, 128.1, 128.7, 130.6, 137.1, 148.2, 155.1, 157.9, 166.8.

Workup

  1. customthe layers were separated
  2. washthe organic phase was washed with water (20 mL) and brine (10 mL)
  3. dry with materialthen dried (Na2SO4)
  4. customevaporated
  5. customThe crude material was chromatographed (silica gel, 1:4 EtOAc/petroleum)

Sources & evidence

ORD record
ord-aefc3fa9d2ff45bc9595f1567d1a39a3
Source dataset
uspto-grants-2007_08
Patent number
US07253194B2

Linked notes

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