Isopropyl chloroformate → Boc-Lysinol(Z)

HRID 1180741ノート

反応式

HRID 1180741 の反応式
C(OC(Cl)=O)(C)C.C(N(CC)CC)C.[CH2:15]([O:22][C:23]([NH:25][CH2:26][CH2:27][CH2:28][CH2:29][C@H:30]([NH:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[C:31](O)=[O:32])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[BH4-].[Na+]>C1(C)C=CC=CC=1.O1CCCC1.O>[C:38]([O:37][C:35]([NH:34][C@H:30]([CH2:31][OH:32])[CH2:29][CH2:28][CH2:27][CH2:26][NH:25][C:23](=[O:24])[O:22][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)=[O:36])([CH3:41])([CH3:40])[CH3:39]

参加物

8

反応物 4

HCID 7917Isopropyl chloroformateHCID 8471TriethylamineHCID 2724765Boc-Lys(Z)-OHHCID 4311764Sodium borohydride

生成物 1

HCID 10915530Boc-Lysinol(Z)収率 68.6%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

A solution of 150.0 mL (150.0 mmol) of 1 M isopropylchloroformate in toluene was added dropwise to a solution of 20.9 mL (150.0 mmol) of triethylamine and 57.06 g (150.0 mmol) of (2S)-6-{[(benzyloxy)carbonyl]amino}-2-[(tert-butoxycarbonyl)amino]hexanoic acid in 500 mL of anhydrous tetrahydrofuran at 0° C. After 2 h, the resulting mixture was filtered to remove solids, rinsing with 100 mL of anhydrous tetrahydrofuran. The filtrate was then added dropwise to a stirred solution of 11.35 g (300.0 mmol) of sodium borohydride in 500 mL of 0° C. water. The cold bath was removed, and the resulting mixture was stirred for 18 h. It was then diluted with 800 mL of ethyl acetate and 300 mL of saturated aqueous sodium bicarbonate. The two layers were separated, the aqueous layer was extracted with two 250 mL aliquots of ethyl acetate, and the extracts were combined with the original ethyl acetate layer. The combined ethyl acetate phase was washed with three 100 ml portions of saturated aqueous sodium bicarbonate, dried over magnesium sulfate, and concentrated under vacuum. The yellow oil was further purified by column chromatography on silica gel, eluting with 4:1 ethyl acetate:hexane to afford 37.70 g (68%) of benzyl (5S)-5-{[t-butyloxycarbonyl]amino}-6-hydroxyhexylcarbamate. 1H NMR (300 MHz, DMSO-d6) δ 7.43-7.30 (m, 5H), 7.25 (t, J=5 Hz, 1H), 6.45 (d, J=8 Hz, 1H), 5.02 (s, 2H), 4.57 (br s, 1H), 3.35-3.29 (m overlapping water peak, 2H), 3.26-3.16 (m, 1H), 3.04-2.93 (m, 2H), 1.39 (s, 9H), 1.57-1.16 (m, 6H). ES-LCMS m/z 389 (M+Na).

後処理

  1. filtrationthe resulting mixture was filtered
  2. customto remove solids
  3. washrinsing with 100 mL of anhydrous tetrahydrofuran
  4. customThe cold bath was removed
  5. additionIt was then diluted with 800 mL of ethyl acetate and 300 mL of saturated aqueous sodium bicarbonate
  6. customThe two layers were separated
  7. extractionthe aqueous layer was extracted with two 250 mL aliquots of ethyl acetate
  8. washThe combined ethyl acetate phase was washed with three 100 ml portions of saturated aqueous sodium bicarbonate
  9. dry with materialdried over magnesium sulfate
  10. concentrationconcentrated under vacuum
  11. customThe yellow oil was further purified by column chromatography on silica gel
  12. washeluting with 4:1 ethyl acetate

出典と根拠

ORDレコード
ord-4fd8107364dd433aaabc238acec10ae5
出典データセット
uspto-grants-2007_10
特許番号
US07282512B2

反応ノート

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